Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
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Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.63387517
Expression of HIF 1alpha or HIF 2alpha was abrogated by infecting astrocytes with lentiviral particles encoding small interference RNA specific for HIF 1alpha or HIF 2alpha ( siHIF 1alpha or siHIF 2alpha ) . 0.63387517^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Placement of introns differs between HIF1A and EPAS 1 , which encodes the human HIF 2alpha protein . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
To date , virtually nothing is known about the signaling pathways that lead to either EPAS 1 or HIF 1 alpha activation . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
These data suggest that HIF 1 alpha , along with HIF 2 alpha , represents a new subclass of the bHLH PAS superfamily . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Expression of ARNT , ARNT 2 , HIF 1 alpha , HIF 2 alpha and Ah receptor mRNAs in the developing mouse . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Under conditions of hypoxia , the ORF 34 promoter was strongly upregulated by HIF 1 alpha and HIF 2 alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Interestingly , NGF effect was specific for HIF 2 alpha mRNA because it did not affect HIF 1 alpha mRNA levels . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
V 12 ras overexpression resulted in an increase in hypoxia induced HIF 1alpha and HIF 2alpha expression . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
It has previously been established that cobalt causes accumulation of HIF 2alpha and HIF 1alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Availability of HIFs is regulated via posttranslational modification of their alpha subunits ( HIF 1alpha and HIF 2alpha ) . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
HIF 1alpha was expressed within tumour cells in 68 % , HIF 2alpha in 46 % , CA 9 in 78 % and VEGF in 52 % of the cases . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
These proteins include the transcriptional activators HIF 1alpha and HIF 2alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
HIF 1alpha seems to be primarily involved in tubulogenesis and HIF 2alpha in renal vasculogenesis . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The outcome of hypoxia is largely regulated by the hypoxia inducible factors ( HIF 1alpha and HIF 2alpha ) . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Like HIF 1alpha , EPAS 1 binds to and activates transcription from a DNA element originally isolated from the erythropoietin gene and containing the sequence 5 ' GCCCTACGTGCTGTCTCA 3 ' . ^^^ Activation by both HIF 1alpha and EPAS 1 is stimulated by hypoxic conditions . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Endothelial PAS domain protein 1 ( EPAS 1 ) is a recently identified bHLH PAS protein with 48 % identity to HIF 1alpha , raising the question of its role in responses to hypoxia . ^^^ Comparison of the effect of a range of activating and inhibitory stimuli showed striking similarities in the EPAS 1 and HIF 1alpha responses . ^^^ Although major differences were observed in the abundance of EPAS 1 and HIF 1alpha in different cell types , differences in the inducible response were subtle with EPAS 1 protein being slightly more evident in normoxic and mildly hypoxic cells . ^^^ Functional studies in a mutant cell line ( Ka 13 ) expressing neither HIF 1alpha nor EPAS 1 confirmed that both proteins interact with hypoxically responsive targets , but suggest target specificity with greater EPAS 1 transactivation ( relative to HIF 1alpha transactivation ) of the VEGF promoter than the LDH A promoter . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Recently another member of the bHLH PAS family , EPAS 1 has been reported and shares similar properties with HIF 1 alpha , although it is considered endothelial specific . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Endothelial PAS protein 1 ( EPAS 1 ) is a basic helix loop helix Per AHR ARNT Sim transcription factor related to hypoxia inducible factor 1alpha ( HIF 1alpha ) . ^^^ Comparison of EPAS 1 with HIF 1alpha demonstrated a similar organization for both proteins , and for the C terminus defined a conserved RLL motif critical for inducibility . ^^^ Overall , EPAS 1 sequences were less inducible than those of HIF 1alpha , and inducibility was strikingly reduced as their expression level was increased . ^^^ Despite these quantitative differences , EPAS 1 regulation appeared similar to HIF 1alpha , conforming to a model involving the modulation of both protein level and activity , through distinct internal and C terminal domains . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Unlike HIF 1alpha the founding member of the HIF family which is expressed more or less ubiquitously , HIF 2alpha ( also called HRF , HLF and EPAS 1 ) is highly expressed by vascular endothelial cells and was shown to activate the transcription of endothelial cell specific receptor tyrosine kinases ( tie 2 and flk 1 / VEGF receptor 2 ) and of vascular endothelial growth factor ( VEGF ) . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
EPAS 1 shares high homology with hypoxia inducible factor 1alpha ( HIF 1alpha ) and , like HIF 1alpha , has been shown to bind to the HIF 1 binding site and to activate its downstream genes such as vascular endothelial growth factor ( VEGF ) and erythropoietin . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
In this study , we investigated the effect of hypoxia on the expression of hypoxia inducible factor 1alpha ( HIF 1alpha ) and endothelial PAS domain protein 1 ( EPAS 1 ) . ^^^ We showed that EPAS 1 , but not HIF 1alpha , is abundantly expressed in human lung adenocarcinoma A 549 cells . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
To define a gene expression profile indicative of the invasive phenotype , we studied by in situ hybridization the expression of genes encoding several pro and anti angiogenic factors [ hypoxia inducible factor ( HIF 1 alpha ) , EPAS 1 , vascular endothelial growth factor ( VEGF ) , VEGF receptors , angiopoietins and their receptor Tie 2 , five genes of the endothelin system , and thrombospondin 1 ] . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
EPAS 1 shares high homology with hypoxia inducible factor 1alpha ( HIF 1alpha ) and is reported to transactivate vascular endothelial growth factor ( VEGF ) , fetal liver kinase 1 ( Flk 1 ) , and Tie 2 promoters . ^^^ Small interfering RNA targeted to EPAS 1 but not HIF 1alpha attenuated desferrioxamine induced Flt 1 mRNA expression , thus EPAS 1 is thought to play an essential role in hypoxic induction of Flt 1 gene . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Several key observations emerged : 1 ) HIF 1 alpha and 2 alpha mRNA were present in placentas of all gestational ages but with greater variability during early pregnancy ; 2 ) overall , HIF 1 alpha mRNA was expressed at a constant level in all placentas , whereas HIF 2 alpha mRNA increased significantly with gestational age ; 3 ) both HIF 1 alpha and 2 alpha protein decreased significantly with gestational age ; and 4 ) HIF 1 alpha and 2 alpha immunoreactivity were overlapping in cellular distribution being expressed by the syncytiotrophoblast , villous cytotrophoblast , and fetoplacental vasculature with both nuclear and cytoplasmic localization . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The von Hippel Lindau tumor suppressor protein ( pVHL ) regulates the stability of HIF 1 alpha and HIF 2 alpha and thus is pivotal in cellular responses to changes in oxygen tension . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
HIF is primarily regulated through oxygen dependent proteasomal destruction of the regulatory subunit , HIF 1 alpha or HIF 2 alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Hypoxia stabilized HIF 1 alpha and HIF 2 alpha proteins and activated the expression of known hypoxia induced genes , such as vascular endothelial growth factor and tyrosine hydroxylase . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate whether anemia , a putative factor counteracting the efficacy of radiotherapy , up regulates the endogenous markers of intratumoral hypoxia , the hypoxia inducible factors HIF 1 alpha and HIF 2 alpha . ^^^ MATERIALS AND METHODS : Forty two hysterectomy specimens harboring endometrial adenocarcinomas of the endometrioid cell type , stage 1 were investigated immunohistochemically for the expression of HIF 1 alpha , HIF 2 alpha and the down stream inducible expression of vascular endothelial growth factor VEGF . ^^^ RESULTS : There was no significant association between Hb levels and the expression of HIF 1 alpha , HIF 2 alpha or VEGF in our material . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The transactivation activity of HIF complexes requires the recruitment of p300 / CREB binding protein ( CBP ) by HIF 1 alpha and HIF 2 alpha that undergo oxygen dependent degradation . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Remarkably , among a panel of hypoxia inducible genes , responses were critically dependent on Hif 1 alpha but not Hif 2 alpha in both endothelial and breast cancer cells but critically dependent on Hif 2 alpha in renal carcinoma cells . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Identification of potential stroke targets by lentiviral vector mediated overexpression of HIF 1 alpha and HIF 2 alpha in a primary neuronal model of hypoxia . ^^^ Overexpression of the hypoxia induced transcription factor subunits HIF 1 alpha and HIF 2 alpha elevated hypoxia mediated transcription of many known HIF regulated genes well above control levels . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Furthermore , the ability of tumors to upregulate hypoxia regulated molecular pathways may affect radiosensitivity by mechanisms independent of the traditional concept of `` oxygen effect . ' ' METHODS AND MATERIALS : In this study , we investigated whether the preoperative blood hemoglobin levels affect the activation status of hypoxia / angiogenic pathways ( hypoxia inducible factors [ HIF 1 alpha and HIF 2 alpha ] , carbonic anhydrase 9 , differentiated embryo chondrocyte protein , vascular endothelial growth factor , and microvessel density ) , in squamous cell head and neck cancer . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
VHL functions in the destruction of the alpha subunits of the heterodimeric transcription factor , hypoxia inducible factor ( HIF 1 alpha and HIF 2 alpha ) , in normoxic conditions . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
At 5 % O 2 , cells developed a weak hypoxic phenotype and HIF 2 alpha , but not HIF 1 alpha , was acutely stabilized . ^^^ At 1 % O 2 , HIF 2 alpha protein remained present in long term cultures , while HIF 1 alpha was present only transiently . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Using murine embryonic cells lacking cytochrome c , and therefore mitochondrial activity , we show that mitochondrial reactive oxygen species ( mtROS ) are essential for proper O ( 2 ) sensing and subsequent HIF 1 alpha and HIF 2 alpha stabilization at 1 . 5 % O ( 2 ) . ^^^ These results provide genetic evidence indicating that mtROS act upstream of prolyl hydroxylases in regulating HIF 1 alpha and HIF 2 alpha in this O ( 2 ) sensing pathway . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
We find that functionality of complex 3 of the mitochondrial electron transport chain ( ETC ) is required for the hypoxic stabilization of HIF 1 alpha and HIF 2 alpha and that an increase in reactive oxygen species ( ROS ) links this complex to HIF alpha stabilization . ^^^ These results demonstrate that mitochondria function as O ( 2 ) sensors and signal hypoxic HIF 1 alpha and HIF 2 alpha stabilization by releasing ROS to the cytosol . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
There are two distinct hypoxia inducible factors ( HIFs ) that control different gene response pathways and we assessed them both with endogenous markers of hypoxia , hypoxia inducible factor HIF 2 alpha ( HIF 2 ) and carbonic anhydrase CA 9 , an indicator of HIF 1 alpha ( HIF 1 ) function . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Considering these results and that Arnt or Arnt 2 functions as a common partner in the formation of transcriptional regulators with other bHLH / PAS proteins such as AhR , HLF , and HIF 1alpha , the possibility arises that CBP / p300 is extensively involved as a coactivator in the transactivation process by bHLH / PAS ( a conserved sequence motif among Per , Arnt , and Sim ) heterodimer transcription factors through interaction with Arnt or Arnt2 . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The partner PAS proteins of Arnt 3 were searched for by the two hybrid system in yeast , and HIF 1 alpha , HLF , and Clock among various bHLH / PAS proteins were found . ^^^ Gel mobility shift analysis using nuclear extracts from 293T cells cotransfected with Arnt 3 and HIF 1 alpha ( or HLF ) expression plasmids revealed that these complexes specifically bound the hypoxia response element ( HRE ) . ^^^ Coexpression of Arnt 3 and HIF 1 alpha ( or HLF ) in Arnt deficient c 4 cells enhanced transcription of a reporter gene driven by the HRE sequences . ^^^ Transcriptionally active heterodimer formation of an Arnt like PAS protein , Arnt 3 , with HIF 1a , HLF , and clock . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Hypoxia inducible factor 1 alpha ( HIF1alpha ) and its related factor , HLF , activate expression of a group of genes such as erythropoietin in response to low oxygen . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Hypoxia inducible factor 1alpha ( HIF 1alpha ) and the HIF like factor ( HLF ) are two highly related basic Helix Loop Helix / Per Arnt Sim ( bHLH / PAS ) homology transcription factors that undergo dramatically increased function at low oxygen levels . ^^^ Despite strong similarities in their activation mechanisms ( e . g . they both undergo rapid hypoxia induced protein stabilization , bind identical target DNA sequences , and induce synthetic reporter genes to similar degrees ) , they are both essential for embryo survival via distinct functions during vascularization ( HIF 1alpha ) or catecholamine production ( HLF ) . ^^^ We report here that DNA binding by HLF , but not by HIF 1alpha , is dependent upon reducing redox conditions . ^^^ Our data reveal that the hypoxia inducible factors are subject to complex redox control mechanisms that can target discrete regions of the proteins and are the first to establish a discriminating control mechanism for differential regulation of HIF 1alpha and HLF activity . . ^^^ Hypoxia inducible factor 1alpha ( HIF 1alpha ) and the HIF like factor ( HLF ) are two highly related basic Helix Loop Helix / Per Arnt Sim ( bHLH / PAS ) homology transcription factors that undergo dramatically increased function at low oxygen levels . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
As well as HIF 1alpha , HIF 2alpha forms a heterodimeric complex with the aryl hydrocarbon receptor nuclear translocator and upregulates hypoxia inducible genes such as vascular endothelial growth factor . ^^^ We found in this study that using green fluorescent protein ( GFP ) fusion constructs , the subcellular localization of HIF 2alpha was different from that of HIF 1alpha in bovine arterial endothelial cells ( BAEC ) . ^^^ The regulation of HIF 2alpha might differ from that of HIF 1alpha in BAEC . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The expression and distribution of the hypoxia inducible factors HIF 1alpha and HIF 2alpha in normal human tissues , cancers , and tumor associated macrophages . ^^^ Hypoxia inducible factors 1alpha and 2alpha ( HIF 1alpha and HIF 2alpha ) are known to dimerize with the aryl hydrocarbon receptor nuclear translocator in mediating this response . ^^^ Because regulation of the alpha chain protein level is a primary determinant of HIF activity , our aim was to investigate the distribution of HIF 1alpha and HIF 2alpha by immunohistochemistry in normal and pathological tissues using monoclonal antibodies ( mAb ) . ^^^ We raised a new mAb to detect HIF 1alpha , designated 122 , and used our previously validated mAb 190b to HIF 2alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Up regulation of hypoxia inducible factors HIF 1alpha and HIF 2alpha under normoxic conditions in renal carcinoma cells by von Hippel Lindau tumor suppressor gene loss of function . ^^^ HIF 1alpha shares 48 per cent identity with the recently identified HIF 2alpha protein that is also stimulated by hypoxia . ^^^ In this study , we analysed the expression of the hypoxia inducible factors HIF 1alpha and HIF 2alpha in a range of VHL wildtype and VHL deficient RCC cell lines . ^^^ In the presence of functional VHL protein , HIF 1alpha mRNA levels are elevated , whereas HIF 2alpha mRNA expression is increased only in cells lacking a functional VHL gene product . ^^^ On the protein levels , however , in VHL deficient cell lines , both HIF alpha subunits are constitutively expressed , whereas re introduction of a functional VHL gene restores the instability of HIF 1alpha and HIF 2alpha proteins under normoxic conditions . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Expression of HIF 1alpha and HIF 2alpha and their effects on survival under hypoxia were studied in six human breast cancer cell lines . ^^^ All of the cell lines studied expressed HIF 1alpha at various levels , but HIF 2alpha was low or absent from the more aggressive cell lines . ^^^ There was an inverse correlation between HIF 1alpha and HIF 2alpha induction and clonogenic survival under hypoxia . ^^^ Thus , cell lines with reduced induction of HIF 1alpha or HIF 2alpha showed high basal levels of VEGF and improved survival under hypoxia . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Using recently produced MoAbs , we examined the expression of HIF1a and HIF2a in a series of 37 early stage esophageal cancers treated with PDT and with additional radiotherapy in case of incomplete response after PDT . ^^^ Strong expression of the HIF1a and of HIF2a proteins in all optical fields examined was noted in 51 % and in 13 % of cases , respectively . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The VCBCR complex binds HIF 1alpha and HIF 2alpha , transcription factors critically involved in cellular responses to hypoxia , and targets them for ubiquitin mediated proteolysis . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
In contrast to HIF 1alpha deficiency , loss of HIF 2alpha did not protect ES cells against apoptosis during hypoxia . ^^^ Both HIF 1alpha ( / ) and HIF 2alpha ( / ) ES cells were , however , resistant to apoptosis in response to hypoglycemia . ^^^ Thus , HIF 1alpha and HIF 2alpha may have distinct roles in responses to environmental stress , and despite its name , HIF 2alpha may be more important in the survival response to environmental variables other than the level of oxygen . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Cotransfection experiments clearly showed that the transcriptional induction of the p75TNFR gene is independent of the hypoxia induced factors , HIF 1alpha and HIF 2alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Whereas HIF 1alpha is expressed ubiquitously , HIF 2alpha is found primarily in the endothelium , similar to endothelin 1 ( ET 1 ) and fms like tyrosine kinase 1 ( Flt 1 ) , the expression of which is controlled by HREs . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
In normal cells the product of the VHL tumour suppressor gene targets the regulatory HIF subunits ( HIF 1alpha and HIF 2alpha ) for oxygen dependent proteolysis , acting as the substrate recognition component of an E 3 ubiquitin ligase . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Transcriptional activation of a proximal VEGF promoter luciferase construct was greatly enhanced by cotransfection with an HIF 2alpha , but not an HIF 1alpha , construct . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
METHODS : HIF 1alpha , HIF 2alpha and HIF 1beta were immunolocalized in cycling endometrium . ^^^ RESULTS : HIF 1alpha and HIF 2alpha were detected in only some endometrial samples , and not confined to the perimenstrual tissue . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Mammals have at least three different HIF alpha subunits , paralogous proteins expressed in tissue specific fashion ( HIF 1alpha , HIF 2alpha , and HIF 3alpha ) . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The kidney demonstrates a marked potential for upregulation of HIF , but accumulation of HIF 1alpha and HIF 2alpha is selective with respect to cell type , kidney zone , and experimental conditions , with the expression patterns partly matching known oxygen profiles . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Hypoxia inducible factor ( HIF1A and HIF2A ) , angiogenesis , and chemoradiotherapy outcome of squamous cell head and neck cancer . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The goal of this study was to examine expression of HIF 1alpha , HIF 2alpha , and NRF 1 and the genes they regulate in pre and postnatal myocardium . ^^^ Steady state mRNA and protein levels of HIF 1alpha and NRF 1 and protein levels of HIF 2alpha were measured along with mRNA of HIF 1alpha regulated genes ( aldolase A , alpha and beta enolase , lactate dehydrogenase A , liver and muscle phosphofructokinase ) and NRF 1 regulated genes ( cytochrome c , Va subunit of cytochrome oxidase , and carnitine palmitoyltransferase 1 ) . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Recently , it is shown that hypoxia induces the expression of hypoxia inducible factor 1alpha and 2alpha ( HIF 1alpha and HIF 2alpha ) , which then up regulates the expression of downstream genes such as carbonic anhydrase 9 ( CA 9 ) and vascular endothelial growth factor ( VEGF ) . ^^^ EXPERIMENTAL DESIGN : We examined the expression of HIF 1alpha , HIF 2alpha , CA 9 , and VEGF by immunohistochemistry in nasopharyngeal carcinoma ( NPC ) biopsies from 90 consecutive patients recruited between 1994 and 1997 in a randomized controlled trial of chemoradiation in locally advanced NPC and investigated their relationship with survival . ^^^ RESULTS : HIF 1alpha was expressed in 52 of 90 ( 58 % ) , HIF 2alpha in 6 of 89 ( 7 % ) , CA 9 in 51 of 90 ( 57 % ) , and VEGF in 54 of 90 ( 60 % ) of tumors . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Here , employing a novel hydroxylation specific antibody , we directly show that proline 564 of HIF 1alpha and proline 531 of HIF 2alpha are hydroxylated under normoxia . ^^^ Importantly , HIF 1alpha Pro 564 and HIF 2alpha Pro 531 hydroxylation is diminished with the treatment of hypoxia , cobalt chloride , desferrioxamine , or dimethyloxalyglycine , regardless of the E 3 ubiquitin ligase activity of the von Hippel Lindau ( VHL ) tumor suppressor gene . ^^^ Furthermore , in VHL deficient cells , HIF 1alpha Pro 564 and HIF 2alpha Pro 531 had detectable amounts of hydroxylation following transition to hypoxia , indicating that the post translational modification is not reversible . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Hypoxia inducible transcription factor subtypes ( HIF 1alpha , HIF 2alpha , HIF 3alpha ) and its dependent target genes , carrying the hypoxia responsive element as regulatory component , were strongly activated in both hypoxic FBPA and SMCPA . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
BACKGROUND : Hypoxia inducible factor 1alpha ( HIF 1alpha ) and HIF 2alpha are essential regulatory proteins for the adaptation of tumor cells to hypoxia , and they stimulate angiogenesis through activation of the vascular endothelial growth factor ( VEGF ) gene . ^^^ METHODS : HIF 1alpha and HIF 2alpha proteins were studied immunohistochemically in a group of 81 patients with Stage 1 endometrial adenocarcinoma of the endometrioid cell type . ^^^ In addition , a sample of 25 normal endometria at various phases of the menstrual cycle was studied for the presence of HIF 1alpha and HIF 2alpha . ^^^ HIF 2alpha protein showed a pattern of expression similar to the pattern seen in HIF 1alpha , but expression of HIF 2alpha protein occurred in only 17 % of endometrial carcinomas , and it was associated with increased TP reactivity . ^^^ There also was a relation of HIF 1alpha expression with well differentiated endometrial neoplasms , and there was a marginal association of HIF 1alpha and HIF 2alpha with ER expression . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
DFE induced HIF 1alpha and HIF 2alpha transcription factors regulating the hypoxic response in the breast tumor cell line MDA 468 . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Here we show that the endothelial basic helix loop helix PAS domain transcription factor , hypoxia inducible factor 2alpha ( HIF 2alpha ) ( but not its close relative HIF 1alpha ) , cooperates with Ets 1 in activating transcription of the vascular endothelial growth factor receptor 2 ( VEGF 2 ) gene ( Flk 1 ) . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Using pharmacological , molecular , and genetic approaches , we also observed that although progesterone primarily up regulates uterine HIF 1alpha expression , estrogen transiently stimulates that of HIF 2alpha . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Their regulation occurs through oxygen dependent proteolysis of the alpha subunits HIF 1alpha and HIF 2alpha , respectively . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The von Hippel Lindau protein ( pVHL ) mediates the ubiquitination and rapid degradation of HIF alpha ( including HIF 1alpha and HIF 2alpha ) . ^^^ It has previously been established that cobalt mimics hypoxia and causes accumulation of HIF 1alpha and HIF 2alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
In response to hypoxia , stabilized HIF 1alpha and HIF 2alpha proteins bind HIF 1beta and initiate expression of genes that alleviate hypoxic stress , including those promoting neovascularization . ^^^ Because VEGF is highly expressed by metanephric podocytes and collecting ducts , developing mouse kidney was examined for the presence and distribution of HIF 1alpha , HIF 2alpha , and HIF 1beta . ^^^ The expression of HIF 1alpha and HIF 2alpha mRNAs in newborn mouse kidney was confirmed by RT PCR and Northern blot analysis . ^^^ By in situ hybridization , HIF 1alpha and HIF 2alpha mRNAs were highly expressed in the nephrogenic zone of newborn kidney cortex and in the medulla . ^^^ Both HIF 1 and HIF 2 heterodimers were identified in newborn kidney lysates by immunoprecipitation with HIF 1alpha , HIF 2alpha , and HIF 1beta antibodies and Western blots . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Endothelial cells ( EC ) express both hypoxia inducible factor 1alpha ( HIF 1alpha ) and 2alpha ( HIF 2alpha ) , yet their roles in the EC hypoxic response are unclear . ^^^ We compared the upregulation of GAPDH in human lung microvascular EC to that in hep3B cells , another cell type known to express both HIF 1alpha and HIF 2alpha . ^^^ Correspondingly , electrophoretic mobility supershift assays showed that , in EC , there was preferential binding of HIF 2alpha to the GAPDH HRE while , in hep3B cells , there was binding of both HIF 1alpha and HIF 2alpha . ^^^ These findings suggest that cell specific patterns of HIF 1alpha and HIF 2alpha expression lead to cell specific gene upregulation during hypoxia . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
HIF 2alpha is a homologue of HIF 1alpha and is abundantly expressed in the lung , but its role in pulmonary hypertension remains unknown . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
We investigated the immunohistochemical expression of HIF 1alpha and HIF 2alpha in the synovium of 22 patients with RA , 34 patients with OA and 22 ' normal ' nonarthritic individuals , in relation to VEGF , VEGF / KDR ( kinase insert domain protein receptor ) vascular activation , PD ECGF and bcl 2 . ^^^ A significant cytoplasmic and nuclear overexpression of HIF 1alpha and HIF 2alpha was noted in the synovial lining and stromal cells of both diseases relative to normal . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Hypoxia induced gene expression occurs solely through the action of hypoxia inducible factor 1alpha ( HIF 1alpha ) : role of cytoplasmic trapping of HIF 2alpha . ^^^ The hypoxia inducible factors 1alpha ( HIF 1alpha ) and 2alpha ( HIF 2alpha ) have extensive structural homology and have been identified as key transcription factors responsible for gene expression in response to hypoxia . ^^^ We show that oxygen dependent protein degradation is restricted to HIF 1alpha , as HIF 2alpha protein is detected in MEFs regardless of oxygenation and is localized primarily to the cytoplasm . ^^^ We show that the factor inhibiting HIF 1 can selectively inhibit the transcriptional activity of HIF 1alpha but has no effect on HIF 2alpha mediated transcription in MEFs . ^^^ We propose that HIF 2alpha is not a redundant transcription factor of HIF 1alpha for hypoxia induced gene expression and show evidence that there is a cell type specific modulator ( s ) that enables selective activation of HIF 1alpha but not HIF 2alpha in response to low oxygen stress . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Ibuprofen mediated reduction of hypoxia inducible factors HIF 1alpha and HIF 2alpha in prostate cancer cells . ^^^ PURPOSE : Hypoxia inducible factors HIF 1alpha and HIF 2alpha are considered to be potential targets for antineoplastic therapy because they regulate the expression of genes that contribute to tumor cell survival , aggressiveness , and angiogenesis . ^^^ RESULTS : Exposure of PC 3 and DU 145 cells to hypoxic condition up regulated HIF 1alpha and HIF 2alpha proteins . ^^^ Treatment with Ibu under normoxic and hypoxic conditions reduced the level of HIF 1alpha and HIF 2alpha . ^^^ Other nonspecific NSAIDs , diclofenac and ketorolac , also inhibited HIF 1alpha and HIF 2alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
To test whether known HIF 1 and HIF 2 are involved in hypoxia induced heNOS promoter activation , HMEC 1 and HUVEC were transiently transfected with HIF 1alpha and HIF 1beta or HIF 2alpha and HIF 1beta expression vectors . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
ANIMAL ( S ) : Forty Swiss / 129SvJ wild type mice and transgenic mice partially deficient for the genes encoding for HIF 1alpha ( HIF 1alpha ( + / ) ) or HIF 2alpha ( HIF 2alpha ( + / ) ) . ^^^ RESULT ( S ) : In both HIF 1alpha and HIF 2alpha wild type mice , pneumoperitoneum enhanced adhesion formation . ^^^ In comparison with wild type mice , basal adhesions were lower in HIF 1alpha ( + / ) and similar in HIF 2alpha ( + / ) mice . ^^^ Pneumoperitoneum did not enhance adhesion formation in HIF 1alpha ( + / ) or in HIF 2alpha ( + / ) mice . ^^^ Therefore , in comparison with the correspondent wild type mice , pneumoperitoneum enhanced adhesions were lower in HIF 1alpha ( + / ) and HIF 2alpha ( + / ) mice . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Differential roles of hypoxia inducible factor 1alpha ( HIF 1alpha ) and HIF 2alpha in hypoxic gene regulation . ^^^ The HIF 1alpha and HIF 2alpha subunits are structurally similar in their DNA binding and dimerization domains but differ in their transactivation domains , implying they may have unique target genes . ^^^ Previous studies using Hif 1alpha ( / ) embryonic stem and mouse embryonic fibroblast cells show that loss of HIF 1alpha eliminates all oxygen regulated transcriptional responses analyzed , suggesting that HIF 2alpha is dispensable for hypoxic gene regulation . ^^^ To address this discrepancy , and to identify specific HIF 2alpha target genes , we used DNA microarray analysis to evaluate hypoxic gene induction in cells expressing HIF 2alpha but not HIF 1alpha . ^^^ In addition , we engineered HEK 293 cells to express stabilized forms of HIF 1alpha or HIF 2alpha via a tetracycline regulated promoter . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
We show that HIF 1alpha , but not HIF 2alpha , binds to a putative HIF responsive element in the Nur 77 promoter , activating the expression of Nur 77 . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Analysis of mice heterozygous for a knockout allele at the locus encoding the O ( 2 ) regulated HIF 1alpha or HIF 2alpha subunit has revealed that these proteins are required for multiple physiological responses to chronic hypoxia , including erythrocytosis and pulmonary vascular remodeling . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Because HIMF gene is upregulated by hypoxia and contains a hypoxia inducible transcription factor ( HIF ) binding site , we subsequently investigated whether HIMF was coexpressed with HIF 2alpha or HIF 1alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Western blot analyses were used to evaluate HIF 1alpha , HIF 1beta , HIF 2alpha , von Hippel Lindau protein , VEGF , Flt 1 , enolase , and GAPDH . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Activation of the hypoxia inducible factor alpha subunits , HIF 1alpha and HIF 2alpha , seems to be subject to similar regulatory mechanisms , and transgene approaches suggested partial functional redundancy . ^^^ Surprisingly , most genes tested were responsive only to the HIF 1alpha siRNA , showing no effect by HIF 2alpha knock down . ^^^ In 786 0 cells lacking HIF 1alpha protein , the identified HIF 1alpha target genes were regulated by HIF 2alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
A progressive increase of HIF 2alpha but not HIF 1alpha occurred in areas remote from the infarct , including the interventricular septum . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Here we show using suppression by small interference RNA that each of the three PHD isoforms contributes in a non redundant manner to the regulation of both HIF 1alpha and HIF 2alpha subunits and that the contribution of each PHD under particular culture conditions is strongly dependent on the abundance of the enzyme . ^^^ In addition , the PHDs manifest specificity for different prolyl hydroxylation sites within each HIF alpha subunit , and a degree of selectively between HIF 1alpha and HIF 2alpha isoforms , indicating that differential PHD inhibition has the potential to selectively alter the characteristics of HIF activation . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
HDAC 7 bound solely to HIF 1alpha among other HIF alpha family members , including HIF 2alpha and HIF 3alpha , whereas HIF 1alpha only interacted with HDAC 7 in the class 2 HDAC family . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
While hypoxia induced the transcription factor hypoxia inducible factor 1alpha ( HIF 1alpha ) in all endothelial cells tested , the closely related HIF 2alpha protein was markedly induced in microvascular / capillary endothelial cells , but only weakly or not at all in artery and vein endothelial cells . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The aim of the present study is to investigate whether hypoxia inducible factors ( HIF 1alpha , HIF 2alpha , HIF 1beta ) are involved in enhanced apoptosis in the human placenta from pregnancies with fetal growth restriction ( FGR ) . ^^^ The expressions of HIF 1alpha , HIF 2alpha , and HIF 1beta were examined by immunohistochemical analysis . ^^^ There were no significant differences in the intensity of the staining for HIF 1alpha and HIF 1beta expressions between two groups , while HIF 2alpha was overexpressed in the placenta from pregnancies with FGR group ( P < 0 . 05 ) . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The expression of vascular endothelial growth factor ( VEGF ) , HIF 1alpha , HIF 2alpha and carbonic anhydrase 9 ( CA 9 ) was examined by immunohistochemistry in 45 patients with PETs and compared to microvascular density ( MVD ) , endothelial proliferation , tumour stage and survival . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
EXPERIMENTAL DESIGN : In this study , we examined HIF [ HIF 1alpha ( HIF 1 ) and HIF 2alpha ( HIF 2 ) ] expression in 87 curatively resected colorectal carcinoma samples , and the results were correlated with clinicopathological factors , microvessel density , cyclooxygenase 2 expression , and patient prognosis . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Impairments in HIF signaling , involving either HIF 1alpha or HIF 2alpha , may play a prominent role in conditions involving altered hematopoietic or erythropoietin homeostasis . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The hypoxia inducible factors 1alpha ( HIF 1alpha ) and 2alpha ( HIF 2alpha ) are key regulators of the transcriptional response to low oxygen and are closely related in domain architecture , DNA binding , and activation mechanisms . ^^^ Here we report on the novel and specific interaction of HIF 2alpha , but not HIF 1alpha , with the NF kappaB essential modulator ( NEMO ) using immunoprecipitation , mammalian two hybrid , and in vitro protein interaction assays . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
METHODS : A multi insult rat model of ARF combining the application of contrast medium with nitric oxide synthase ( NOS ) and cyclooxygenase ( COX ) inhibition was used to study chronology and distribution of the oxygen regulated HIF isoforms HIF 1alpha and HIF 2alpha in comparison with the hypoxia marker pimonidazole between 10 minutes and 48 hours after injury induction . ^^^ HIF isoforms were expressed in a cell type specific fashion : HIF 1alpha in tubular and HIF 2alpha in interstitial and endothelial cells . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Stimulation of HIF 1alpha , HIF 2alpha , and VEGF by prolyl 4 hydroxylase inhibition in human lung endothelial and epithelial cells . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
HIF activity is regulated by hypoxic stabilization of the related HIF 1alpha and HIF 2alpha subunits , which are frequently overexpressed in cancer cells . ^^^ To assess the relative tumor promoting functions of HIF 1alpha and HIF 2alpha directly , we replaced HIF 1alpha expression with HIF 2alpha by creating a novel `` knock in ' ' allele at the Hif 1alpha locus through homologous recombination in primary murine embryonic stem cells . ^^^ These and other data indicate that HIF 2alpha promotes tumor growth more effectively than HIF 1alpha in multiple contexts . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Of these , 21 were elevated both by transfection with HIF 1alpha and with HIF 2alpha , and 14 were preferentially activated by HIF 1alpha including several involved in glycolysis . ^^^ An additional 10 genes were up regulated by hypoxia but minimally activated by HIF 1alpha or HIF 2alpha transfection . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Hypoxia inducible factor 1alpha ( HIF 1alpha ) and HIF 2alpha protein expression was monitored in parallel . ^^^ Hypoxia inducible factor 1alpha ( HIF 1alpha ) and HIF 2alpha protein expression was monitored in parallel . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
We have investigated the possibility that the hypoxia inducible factors HIF 1alpha and HIF 2alpha , which are activated by oxygen deprivation , are involved in this resetting process . ^^^ Accordingly , we used immunostaining and densitometry to quantitate the levels of the HIF 1alpha and HIF 2alpha proteins in the rat CB during early perinatal life and after exposure to in vivo hypoxia during adolescence . ^^^ After exposure to hypoxia ( 8 % O ( 2 ) , 6 h ) , the expression of HIF 1alpha was selectively up regulated in glomus cells and apparent translocation of both HIF 1alpha and HIF 2alpha to the nucleus was observed . ^^^ During the first postnatal week , the intensity of immunostaining for HIF 1alpha in glomus cells decreased markedly , whereas the level of HIF 2alpha remained constant . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The 2alpha form of HIF ( HIF 2alpha ) , but not HIF 1alpha , drives in vitro and in vivo tumorigenesis of VHL / RCC cells by specifically activating the TGF alpha / EGFR pathway . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Defective function of the von Hippel Lindau ( VHL ) tumor suppressor ablates proteolytic regulation of hypoxia inducible factor alpha subunits ( HIF 1alpha and HIF 2alpha ) , leading to constitutive activation of hypoxia pathways in renal cell carcinoma ( RCC ) . ^^^ Here we report a comparative analysis of the functions of HIF 1alpha and HIF 2alpha in RCC and non RCC cells . ^^^ We also show that HIF alpha isoforms display unexpected suppressive interactions in RCC cells , with enhanced expression of HIF 2alpha suppressing HIF 1alpha and vice versa . ^^^ In VHL defective RCC cells , we demonstrate that the protumorigenic genes encoding cyclin D 1 , transforming growth factor alpha , and vascular endothelial growth factor respond specifically to HIF 2alpha and that the proapoptotic gene encoding BNip 3 responds positively to HIF 1alpha and negatively to HIF 2alpha , indicating that HIF 1alpha and HIF 2alpha have contrasting properties in the biology of RCC . ^^^ In keeping with this , HIF alpha isoform specific transcriptional selectivity was matched by differential effects on the growth of RCC as tumor xenografts , with HIF 1alpha retarding and HIF 2alpha enhancing tumor growth . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
METHODS : Twenty five cutaneous capillary haemangiomas , excised from patients under 14 years of age , were studied immunohistochemically for endothelial cells , the angiogenic factors thymidine phosphorylase ( TP ) and vascular endothelial growth factor ( VEGF ) , the proliferation index Ki 67 , and the hypoxia inducible factors 1alpha ( HIF 1alpha ) and 2alpha ( HIF 2alpha ) . ^^^ Between 5 and 20 % of the endothelial cells were Ki 67 positive , indicating an intense proliferative activity ; more importantly , they consistently expressed VEGF and HIF 2alpha , and in many cases TP , but failed to react with HIF 1alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The hypoxia inducible transcription factors HIF 1alpha and HIF 2alpha are activated in hypoxic tumor regions . ^^^ However , their role in tumorigenesis remains controversial , as tumor growth promoter and suppressor activities have been ascribed to HIF 1alpha , while the role of HIF 2alpha remains largely unknown . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The recently identified third member of the human HIF alpha family , HIF 3alpha , produces multiple splice variants that contain extra DNA binding elements and protein protein interaction motifs not found in HIF 1alpha or HIF 2alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
HIF 2alpha is a homologue of the HIF 1alpha transcription factor , both of which play a role in the activation of a number of hypoxia responsive genes . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Transfection experiments demonstrated that especially HIF 3alpha and HIF 2alpha , and to a lesser extent HIF 1alpha , contribute to the induction of IGFBP 1 mRNA expression in isolated hepatocytes , whereas experiments with vectors for the HIF prolyl hydroxylases ( PHD ) indicated a major role of PHD 2 in destabilization of HIFs , attenuating the induction of IGFBP 1 under venous pO ( 2 ) . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Because hypoxia is frequently associated with acidosis , like in ischemia or tumour growth , we studied the impact of acidosis on the expression of the HIF 1alpha and HIF 2alpha proteins and that of the three HIF target genes carbonic anhydrase 9 ( CA 9 ) , glucose transporter 1 ( Glut 1 ) and erythropoietin ( EPO ) . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
To examine the expression patterns of all HIF alpha subunits ( HIF 1alpha , HIF 2alpha and HIF 3alpha ) in pulmonary arteries of rats undergoing systemic hypoxia , five groups of healthy male Wistar rats were exposed to normoxia ( N ) and hypoxia for 3 ( H 3 ) , 7 ( H 7 ) , 14 ( H 14 ) and 21 ( H 21 ) d respectively . ^^^ A substantial alteration of HIF 1alpha and HIF 3alpha staining occurred in pulmonary arteries after 14 d and 7 d of hypoxia , respectively , but HIF 2alpha staining showed an inversed trend after 14 d of hypoxia . ^^^ Our study found that HIF 1alpha , HIF 2alpha and HIF 3alpha may not only confer different target genes , but also play key pathogenetic roles in hypoxic induced pulmonary hypertension . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Expression of HIF 1alpha protein by Western blotting of nuclear extracts of fetal baboon samples differed from that of HIF 2alpha in that both were high at early third trimester , but at term , HIF 1alpha was absent , whereas HIF 2alpha remained unchanged . ^^^ HIF 1alpha was diminished both in 125 day and 140 day BPD models , whereas HIF 2alpha was reduced only in the latter . ^^^ Surprisingly , vascular endothelial growth factor ( VEGF ) was enhanced in preterm baboons with BPD as compared with age matched fetal controls , and there was a negative correlation between HIF 1alpha and / or HIF 2alpha and VEGF in BPD . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The C terminal activation domain ( C TAD ) of the hypoxia inducible transcription factors HIF 1alpha and HIF 2alpha binds the CH 1 domains of the related transcriptional coactivators CREB binding protein ( CBP ) and p 300 , an oxygen regulated interaction thought to be highly essential for hypoxia responsive transcription . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Impact of HIF 1alpha and HIF 2alpha on proliferation and migration of human pulmonary artery fibroblasts in hypoxia . ^^^ Hypoxia induced a marked up regulation ( protein level ) of both HIF 1alpha and HIF 2alpha , alongside with nuclear translocation of these transcription factors . ^^^ Specific inhibition of either HIF 1alpha or HIF 2alpha was achieved by RNA interference technology , as proven by HIF 1alpha and HIF 2alpha mRNA and protein analysis and expression analysis of HIF downstream target genes . ^^^ With the use of this approach , the hypoxia induced proliferative response of the FBPA was found to be solely HIF 2alpha dependent , whereas the migratory response was significantly reduced by both HIF 1alpha and HIF 2alpha interference . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
This control is achieved by hypoxia inducible transcription factors ( HIF ) , consisting of a constitutive beta subunit and one of two alternative oxygen regulated HIFalpha subunits ( HIF 1alpha and HIF 2alpha ) . ^^^ Although HIF 1alpha was the first transcription factor identified through its ability to bind to an enhancer sequence of the EPO gene , more recent evidence suggests that HIF 2alpha is responsible for the regulation of EPO . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Regular endurance training reduces the exercise induced HIF 1alpha and HIF 2alpha mRNA expression in human skeletal muscle in normoxic conditions . ^^^ With hypoxic exposure , HIF 1alpha and HIF 2alpha protein are stabilized . ^^^ Considering that several of these genes are also induced with exercise , we tested the hypothesis that the mRNA level of HIF 1alpha and HIF 2alpha subunits increases with a single exercise bout , and that this response is blunted with training . ^^^ In the untrained leg , the exercise bout induced an increase ( P < 0 . 05 ) in HIF 1alpha fold and HIF 2alpha fold mRNA at 6 h of recovery . ^^^ In contrast , HIF 1alpha and HIF 2alpha mRNA levels were not altered at any time point in the trained leg . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Nickel exposure caused strong activation of HIF 1alpha and HIF 2alpha proteins , underscoring activation of HIF 1 dependent transcription . ^^^ In contrast , cell density dependent transcription was characterized by minor induction of HIF 1alpha or HIF 2alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
These results suggest that Cx 32 might reduce PAI 1 , uPA and uPAR production in metastatic RCC cells via the inhibition of Src dependent induction of HIF 1alpha and HIF 2alpha gene expression and that Cx 32 might suppress hypoxia inducible gene expression under hypoxic conditions . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
HUVECs expressed both HIF 1alpha and HIF 2alpha when cultured under hypoxic conditions . ^^^ Transfection of HIF 1alpha , but not HIF 2alpha , siRNA to HUVECs completely abrogated hypoxic induction of cords . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
There was no relationship between TP and HIF 1alpha , but there was a weak borderline significant relationship with HIF 2alpha expression . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Regulation of the level of hypoxia inducible factors 1alpha and 2alpha ( HIF 1alpha and HIF 2alpha ) is a primary determinant of HIF activity . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Knockdown of HIF 1alpha similarly inhibited PDGF stimulated proliferation , whereas HIF 2alpha knockdown had no effect on HPASMC proliferation . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Using a genetic `` knock in ' ' strategy , we demonstrate that targeted replacement of the oxygen regulated transcription factor HIF 1alpha with HIF 2alpha results in expanded expression of HIF 2alpha specific target genes including Oct 4 , a transcription factor essential for maintaining stem cell pluripotency . ^^^ We show that HIF 2alpha , but not HIF 1alpha , binds to the Oct 4 promoter and induces Oct 4 expression and transcriptional activity , thereby contributing to impaired development in homozygous Hif 2alpha KI / KI embryos , defective hematopoietic stem cell differentiation in embryoid bodies , and large embryonic stem cell ( ES ) derived tumors characterized by altered cellular differentiation . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The demonstration that HDAIs repress both HIF 1alpha and HIF 2alpha transactivation potential independently of von Hippel Lindau tumor suppressor and p 53 function indicates that HDAIs may have biological effects in a broad range of tissues in addition to tumors . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
In the normal , fully developed kidney , HIF 1alpha is expressed in most cell types , whereas HIF 2alpha is mainly found in renal interstitial fibroblast like cells and endothelial cells . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Concordant regulation of gene expression by hypoxia and 2 oxoglutarate dependent dioxygenase inhibition : the role of HIF 1alpha , HIF 2alpha , and other pathways . ^^^ Many of these responses were suppressed by short interfering RNAs directed against HIF 1alpha and HIF 2alpha , with HIF 1alpha suppression manifesting substantially greater effects than HIF 2alpha suppression , supporting the importance of HIF pathways . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
To assess if HIF over expression is a prominent feature of other renal cell carcinoma histological subtypes we characterized the expression of HIF 1alpha and HIF 2alpha in genetically distinct early renal cortical tumors . ^^^ RESULTS : Clear cell RCC tumors from patients with von Hippel Lindau disease strongly expressed HIF 1alpha and HIF 2alpha ( 10 of 12 and 12 of 12 tumors , respectively ) . ^^^ Chromophobe tumors from patients with Birt Hogg Dub syndrome expressed predominantly HIF 2alpha with weaker HIF 1alpha expression ( 12 of 12 and 6 of 12 tumors , respectively ) . ^^^ CONCLUSIONS : Differential patterns of HIF 1alpha and HIF 2alpha protein over expression were found among the 3 human kidney tumor types associated with multifocal hereditary kidney tumor syndromes . ^^^ Consistent , simultaneous over expression of HIF 1alpha and HIF 2alpha appears to be specific to VHL negative clear cell renal cell carcinoma . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Differential regulation of the transcriptional activities of hypoxia inducible factor 1 alpha ( HIF 1alpha ) and HIF 2alpha in stem cells . ^^^ Transcriptional responses to hypoxia are primarily mediated by hypoxia inducible factors ( HIFs ) , HIF 1alpha and HIF 2alpha . ^^^ The HIF 1alpha and HIF 2alpha subunits are structurally similar in their DNA binding and dimerization domains but differ in their transactivation domains , implying they may have unique target genes and require distinct transcriptional cofactors . ^^^ Our previous results demonstrated that HIF 1alpha and HIF 2alpha regulate distinct target genes . ^^^ Using DNA microarray analysis of hypoxia inducible genes in wild type ( WT ) , Hif 1alpha ( ) ( / ) ( ) , and Hif 2alpha ( ) ( / ) ( ) ES cells , we show that HIF 1alpha induces a large number of both confirmed and novel hypoxia inducible genes , while HIF 2alpha does not activate any of its previously described targets . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The deduced gcHIF 1alpha protein is highly similar to the HIF 1alphas ( 57 68 % ) from various vertebrate species , while gcHIF 4alpha is a novel isoform , and shows an equivalent degree of amino acid identity ( 41 47 % ) to the HIF 1alpha , HIF 2alpha and HIF 3alpha proteins so far described . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
OBJECTIVE : To observe the expression of hypoxia inducible factor alpha ( HIF 1alpha , HIF 2alpha , HIF 3alpha ) and pulmonary vascular remodeling in pulmonary arteries of patients with chronic obstructive pulmonary disease ( COPD ) . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
HIF 1alpha , but not HIF 2alpha , mRNA and protein were increased ( 8 and 3 fold , respectively ) in FG 4095 treated baboons relative to untreated controls . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Two transcription factors [ hypoxia inducible factor 1alpha ( HIF 1alpha ) and HIF 2alpha ] are dramatically induced in hypoxic areas and regulate the expression of genes necessary for tumor adaptation to the conditions of low oxygen ; however , the relative contribution of these factors is controversial . ^^^ We used RNA interference mediated inactivation of HIF 1alpha or HIF 2alpha followed by microarray analysis to identify genes specifically regulated by either HIF 1 or HIF 2 in hypoxia . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Despite high similarity with respect to protein sequence and activation pathway , a growing number of physiological and mechanistic differences between HIF 1alpha and HIF 2alpha are being reported . ^^^ We characterize a conserved amino acid substitution between HIF 1alpha and HIF 2alpha that contributes to the intrinsically higher FIH 1 mediated asparaginyl hydroxylation of HIF 1alpha and , hence , lower HIF 1alpha activity . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Hypoxia inducible factor ( HIF ) alpha subunits ( HIF 1alpha , HIF 2alpha and HIF 3alpha ) , which play a pivotal role during the development of hypoxia induced pulmonary hypertension ( HPH ) , are regulated through post translational hydroxylation by their three prolyl hydroxylase domain containing proteins ( PHD 1 , PHD 2 and PHD 3 ) . ^^^ HIF 1alpha and HIF 2alpha mRNA increased slightly after 7 d of hypoxia , but HIF 3alpha increased significantly after 3 d of hypoxia . ^^^ In hypoxic animals , HIF 1alpha proteins negatively correlated with PHD 2 proteins , whereas HIF 2alpha and HIF 3alpha proteins showed negative correlations with PHD 3 and PHD 1 proteins , respectively . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Both pretreatments strongly induced the accumulation of HIF 1alpha and HIF 2alpha in tubular and peritubular cells , respectively , as well as HIF target gene expression . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Overexpression of hypoxia inducible factors ( HIF ) , HIF 1alpha and HIF 2alpha , leads to the up regulation of genes involved in proliferation , angiogenesis , and glucose metabolism and is associated with tumor progression in several cancers . ^^^ However , the contribution of HIF 1alpha versus HIF 2alpha to vascular endothelial growth factor ( VEGF ) expression and other HIF regulated target genes under different conditions is unclear . ^^^ To address this , we used small interfering RNA ( siRNA ) techniques to knockdown HIF 1alpha and / or HIF 2alpha expression in response to hypoxia , insulin like growth factor ( IGF ) 1 , or renal carcinoma cells expressing constitutively high basal levels of HIF 1alpha and / or HIF 2alpha due to loss of von Hippel Lindau ( VHL ) function . ^^^ We found that HIF 1alpha primarily regulates transcriptional activation of VEGF in response to hypoxia and IGF 1 compared with HIF 2alpha in MCF 7 cells . ^^^ We also observed a reciprocal relationship between HIF 1alpha and HIF 2alpha expression in hypoxia in these cells : HIF 2alpha siRNA enhanced HIF 1alpha mediated VEGF expression in MCF 7 cells in response to hypoxia , which could be completely blocked by cotransfection with HIF 1alpha siRNA . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
There are 2 main homologues of the regulatory proteins , HIF 1alpha and HIF 2alpha , which have different effects in genetic knock out experiments . ^^^ METHODS : The expression of HIF 1alpha , HIF 2alpha , carbonic anhydrase 9 ( CA 9 ) , and peripheral hemoglobin ( Hb ) levels in 151 patients who underwent surgery for head and neck squamous cell carcinoma ( HNSCC ) were analyzed and related to outcome . ^^^ RESULTS : High HIF 1alpha was expressed in 45 of 140 tumors ( 30 % ) , HIF 2alpha was expressed in 21 of 139 tumors ( 14 % ) , and CA 9 was expressed in 56 of 149 tumors ( 62 % ) . ^^^ There was a positive correlation between HIF 1alpha expression and HIF 2alpha expression ( P = . 0001 ) . ^^^ Nine percent of tumors expressed both high HIF 1alpha and high HIF 2alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
AIMS : To investigate the significance of the hypoxia inducible factors HIF 1alpha and HIF 2alpha in gallbladder adenocarcinomas and their relation to angiogenesis and to the expression of VEGF , an angiogenic factor transcriptionally regulated by HIFalphas . ^^^ RESULTS : Overexpression of HIF 1alpha and 2alpha was significantly associated with increased tumor angiogenesis and VEGF expression , while HIF 2alpha was linked with upregulation of TP . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
The aryl hydrocarbon receptor nuclear translocator ( Arnt ) , also called Hif 1beta , serves as an obligate heterodimerization partner of Hif 1alpha and Hif 2alpha . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Two families of O serogroups showed antigenic crossreactivities ( PHA , MOP 1 , MOP 2 , MOP 3 , HEL 1 , HEL 2 , and SYR 1 ; PERSAVTOM 1 , PERSAVTOM 2 , DEL , POR , and SYR 2 ) . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Coimmunoprecipitation studies , yeast two hybrid analysis , and transient transfection experiments demonstrated that MOP 1 and MOP 2 dimerize with ARNT and that these complexes are transcriptionally active at defined DNA enhancer sequences in vivo . ^^^ The expression profiles of the AHR , MOP 1 , and MOP 2 mRNAs , coupled with the observation that they all share ARNT as a common dimeric partner , suggests that the cellular pathways mediated by MOP 1 and MOP 2 may influence or respond to the dioxin signaling pathway . . ^^^
Interacting proteins: Q99814 and Q16665	Pubmed	SVM Score :0.0
Whole genome quantitative trait loci mapping of 114 selected pcy / pcy mice ( 68 with the mild PKD and 46 with severe PKD ) identified two loci , MOP 1 and MOP 2 that strongly modulate PKD progression . ^^^ MOP 1 ( max LOD score = 10 . 3 at D4Mit111 ) and MOP 2 ( max LOD score = 13 . 8 at D16Mit1 ) accounted for 36 . 7 and 46 . 8 % of the phenotypic variance , respectively . ^^^ Two factor ANOVA of the phenotypes and genotypes of all 673 pcy / pcy mice from our cross indicated that MOP 1 and MOP 2 alleles regulate PKD progression in a complex additive manner . ^^^