Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.96859123 |
It is postulated that the interactions of Gadd 45 with both p21Cip1 and PCNA are important for the modulation of cell cycles , and for the inhibition of DNA replication . . 0.96859123^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Finally , it was observed that a spectrum of p 53 target genes implicated in p 53 induced growth suppression and apoptosis were similarly regulated , either induced ( gadd 45 , waf 1 , mdm 2 , and bax ) or suppressed ( c myc and bcl 2 ) , after activation of wt p 53 function in M1p53 and M1p53 / bcl 2 cells . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Cytotoxicity and expression of p 53 related genes ( WAF 1 and GADD 45 ) were tested after 24 hours of treatment with different drugs . ^^^ An increase in the transcription of WAF 1 and GADD 45 genes was found in cells expressing p 53 and treated with the drugs . ^^^ GADD 45 and WAF 1 expression was also found in cells not expressing p 53 but treated with the drugs , suggesting that these genes can also be activated by DNA damage through a pathway independent of p 53 . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Adenovirus E1A proteins inhibit activation of transcription by p 53 . p 53 stimulates the transcription of a number of genes , such as MDM 2 , Waf 1 , and GADD 45 . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Several pathologic settings requiring DNA replication and / or DNA repair are dependent upon the expression of p 53 and at least one of two p 53 dependent proteins , termed p 21 ( also called WAF 1 ) and GADD 45 . ^^^ We therefore sought to determine if p 53 , p 21 ( WAF 1 ) or GADD 45 mRNA levels were changed in obstruction . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
With concentrations of each inhibitor able to block DNA synthesis , no induction of message for the cyclin dependent kinase inhibitor waf 1 was observed ; while induction of gadd 45 message indicated that the cells might be responding to growth arrest or DNA damage . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
This increase in p 53 levels led to an increase in the mRNA and protein levels of p 53 downstream genes ( WAF 1 , GADD 45 , and bax ) . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
OP also differentially induces endogenous expression of several known p 53 target genes such as Waf 1 and Mdm 2 , but not Bax , Gadd 45 , and PCNA . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Abnormalities of the tumor suppressor p 53 , which exerts growth suppressing and apoptosis enhancing functions through the transcriptional regulation of downstream genes including CDKN 1 , GADD 45 , and BCL 2 , are also often found . ^^^ Expression levels of p 53 , CDKN 1 , and GADD 45 were moderately and coordinately decreased at 1 day after cessation of MP treatment and remained repressed a week later . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Exposure of cultures of A 549 cells to alpha particles resulted in an increase in the protein levels of the DNA damage inducible genes , p 53 , Cip 1 , and Gadd 45 . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
The immunoreactive expression of wt p 53 , p 53 response proteins ( WAF 1 , Bax and Gadd 45 ) , and a cell cycle protein ( cyclin D ) were detected and preferentially localized to nuclei of apoptotic granule cells , and were weakly expressed in nuclei of necrotic pyramidal CA1 / 2 cells . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
WAF 1 and GADD 45 mRNAs were also increased by DDP treatment , independently of the presence of a wt p 53 . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
These effects of pTpT are accomplished , at least in part , by the up regulation of a set of genes involved in DNA repair ( ERCC 3 and GADD 45 ) and cell cycle inhibition ( SDI 1 ) . ^^^ At least two of these genes ( GADD 45 and SDI 1 ) are known to be transcriptionally regulated by the p 53 tumor suppressor protein . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
We have now identified , partially purified , and characterized an additional approximately 40 kDa nuclear protein , p53CP ( p 53 competing protein ) , that specifically binds to the consensus p 53 binding sites found in several p 53 downstream target genes , including Waf 1 , Gadd 45 , Mdm 2 , Bax , and RGC . ^^^ The minimal sequence requirement for binding is a 14 bp motif , 5 ' CTTGCTTGAACAGG 3 ' [ 5 ' C ( A / T ) ( T / A ) GPyPyPyPuPuPuC ( A / T ) ( T / A ) G 3 ' ] , which includes the central nucleotides of the typical p 53 binding site with one mismatch . p53CP and p 53 ( complexed with antibody ) showed a similar binding specificity to Waf 1 site but differences in Gadd 45 and T3SF binding . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
The kinetics of accumulation of p 53 and two effector proteins involved in cell cycle arrest , WAF 1 and GADD 45 , were also directly related to the repair potential of the cells , as in normal human fibroblasts their levels declined after 24 h , the time required for repair of UV induced lesions , whereas NER deficient TTD / XP D cells showed p 53 , WAF 1 , and GADD 45 accumulation for over 72 h after irradiation . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
However , we detected induction of the p21Cip1 cyclin dependent kinase inhibitor gene during differentiation , which was markedly enhanced in the presence of p 53 . p 53 dependent expression of p21Cip1 occurred in the absence of an increase in p 53 mRNA and protein levels and was specific for p21Cip1 , since expression of gadd 45 , mdm 2 , cyclin G and bax were unaffected by p 53 . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Double staining immunohistochemistry was also used to investigate the relationship between apoptotic cell death and selective protein expression associated with DNA damage and repair ( p 53 , Bax , MDM 2 , WAF 1 , Gadd 45 , PCNA ) and cell cycle protein , Cyclin D 1 , in male Wistar rats 48 h after injury . ^^^ Proteins associated with DNA damage and repair ( p 53 , Bax , MDM 2 , WAF 1 , Gadd 45 , PCNA ) were expressed in the cytoplasm of normal cells of naive and sham rats . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
The constitutive levels of WAF 1 and Gadd 45 , unexpectedly seen in the p 53 deficient Y 8 cells , decreased following doxorubicin treatment . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
These data indicate that there are p 53 independent pathway ( s ) that may still involve WAF 1 and Gadd 45 with respect to cell cycle control and apoptosis . . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Further studies examined the effect of 311 and DFO on the expression of p 53 transactivated genes that are crucial for cell cycle control and DNA repair , namely WAF 1 , GADD 45 , and mdm 2 . ^^^ Incubation of 3 different cell lines with DFO or 311 caused a pronounced concentration and time dependent increase in the expression of WAF 1 and GADD 45 mRNA , but not mdm 2 mRNA . ^^^ In accordance with the distinct differences in Fe chelation efficacy and antiproliferative activity of DFO and 311 , much higher concentrations of DFO ( 150 micromol / L ) than 311 ( 2 . 5 to 5 micromol / L ) were required to markedly increase GADD 45 and WAF 1 mRNA levels . ^^^ The increase in GADD 45 and WAF 1 mRNA expression was seen only after 20 hours of incubation with the chelators and was reversible after removal of the ligands . ^^^ In contrast to the chelators , the Fe ( 3 ) complexes of DFO and 311 had no effect on increasing GADD 45 and WAF 1 mRNA levels , suggesting that Fe chelation was required . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
We found a linear dose response relationship for induction of CDKN1A ( formerly known as CIP1 / WAF1 ) and GADD 45 mRNA levels over the range of 2 50 cGy , with no evidence of a threshold for induction . ^^^ Although exposures to 2 and 5 cGy did not result in any detectable reduction in cloning efficiency or increased apoptosis in ML 1 cells , these exposures did produce a transient delay of cells in the phases of the cell cycle in addition to the observed up regulation of CDKN1A and GADD 45 . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
In this study we have examined the Fe chelation efficacy and antiproliferative activity of these chelators including their effects on the expression of genes ( WAF 1 and GADD 45 ) known to be important in mediating cell cycle arrest at G1 / S . ^^^ In addition , in contrast to 311 , which markedly increased WAF 1 and GADD 45 mRNA expression , PCBH and PCTH did not have any effect , whereas PCBBH increased the expression of GADD 45 mRNA . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
We have utilized mouse embryo fibroblasts ( MEFs ) lacking p 53 genes or downstream effector genes of the p 53 pathway , gadd 45 ( Gadd45a ) or p 21 ( Cdkn1a ) , as well as MEFs lacking both gadd 45 and p 21 genes to address the potential contribution of these downstream effectors to p 53 associated DNA repair . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Furthermore , the assessment of p 53 function after ionizing radiation of ATLL cells indicated an abnormal induction of the p 53 responsive genes GADD 45 and p 21 ( WAF 1 ) in 7 of 7 patients . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Gadd 45 and to a lesser extent Gadd 153 ( stress genes induced by , e . g . , ionizing radiation and ischaemia ) were up regulated , as well as p21waf1 , cip 1 , a protein participating in cell cycle regulation that can interact with Gadd 45 . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
To investigate the consequence of the shear induced p 53 response , we found that prolonged laminar shear stress caused increases of the growth arrest proteins GADD 45 ( growth arrest and DNA damage inducible protein 45 ) and p 21 ( cip 1 ) , as well as a decrease in phosphorylation of the retinoblastoma gene product . ^^^ Our results suggest that prolonged laminar shear stress causes a sustained p 53 activation , which induces the up regulation of GADD 45 and p 21 ( cip 1 ) . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
GADD 45 can interact in vivo with the G ( 2 ) cell cycle specific kinase , Cdc 2 , proliferating cell nuclear antigen ( PCNA ) , and the cell cycle kinase inhibitor p 21 ( waf 1 ) . ^^^ Alanine substitutions in the region abolished GADD 45 induction of a G ( 2 ) / M arrest and its inactivation of the Cdc 2 kinase but not its binding to Cdc 2 , PCNA , or p 21 ( waf 1 ) . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
These deoxyadenosine resistant cells ( Y 8 ) also do not express p 53 protein but do have WAF 1 and Gadd 45 mRNA and protein . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Although chelators induced a marked increase in WAF 1 and GADD 45 mRNA transcripts , there was no appreciable increase in their protein levels . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
However , treatment with 0 . 5 4 mM WR 1065 partially restored wild type conformation at 37 degrees C , stimulated DNA binding activity , and increased the expression of p 53 target genes WAF 1 , GADD 45 , and MDM 2 , leading to cell cycle arrest in G ( 1 ) . ^^^ |
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Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Early induction of CDKN1A ( p 21 ) and GADD 45 mRNA by a low dose of ionizing radiation is due to their dose dependent post transcriptional regulation . ^^^ It is possible that the more rapid induction of the mRNA of the CDKN1A and GADD 45 genes after exposure to 50 cGy of 10 rays than after 20 Gy is due to a lower level of stabilization of the mRNA of these genes after 50 cGy . ^^^ In addition , our results show that 50 cGy of 10 rays increases the transcription rates of the CDKN1A and GADD 45 genes , with a maximum induction at 0 . 5 to 1 h after irradiation , much earlier than the maximum accumulation of stabilized TP 53 protein . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
A semi quantitative RT PCR method was developed to allow the analysis of the expression of 5 p 53 effector genes ( p 21 ( WAF 1 ) , mdm 2 , cyclin G 1 , gadd 45 , bax ) at the same time with a small amount of RNA ( 1 microg ) . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Macroarray analysis confirmed that several p 53 target genes as p 21 ( Waf 1 ) , mdm 2 , gadd 45 , pig 8 , and pig 3 were down regulated at the mRNA level by amifostine in NB 4 and K 562 . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
These included reconfirmation of previously observed associations between mutant and wild type status of p 53 , and chemosensitivity to alkylating agents , while extending these results to reveal associations with gamma induced expressions of MDM 2 , WAF 1 and GADD 45 , signals that were not apparent in measurements of basal mRNA expression levels for any of these genes . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Also , the inability of cell cycle regulatory proteins like PCNA , p 21 ( waf 1 ) , and Gadd 45 to control DNA demethylase activity in cancerous cell lines is discussed in terms of accelerated G ( 1 ) / G ( 2 ) cell cycle stage exit to facilitate unregulated cellular proliferation , loss of control of chromosomal organization , and the development of oncogenesis in cancerous cell lines . . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Very few genes have been found to be consistently up regulated by IR , but that set includes GADD 45 , CDKN1A , and genes associated with the nucleotide excision repair pathway . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
The level of p 53 , p21Cip1 , bax , mdm 2 , cyclin G , gadd 45 genes expression in the liver of mice of different lines given OAT injection was studied by multiplex PCR method . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Exposure to 5 aza CR induced the up regulation of genes promoting cell cycle arrest and DNA repair ( p 21 ( WAF 1 ) and GADD 45 ) or apoptosis ( p 53 , RIPK 2 , Bak 1 , caspase 5 , and caspase 6 ) . ^^^ Co incubation with pifithrin alpha ( PFT alpha ) , a selective p 53 inhibitor , restored GADD 45 , Bcl 2 , cyclin B 1 , and p 21 ( WAF 1 ) expression levels and almost completely reversed the growth inhibitory , cell cycle , and apoptotic effects of 5 aza CR . 5 aza CR treatment caused global demethylation and reactivation of p 16 ( INK 4 ) expression . ^^^ Our data demonstrate that 5 aza CR action in HCT 116 is mediated by p 53 and its downstream effectors p 21 ( WAF 1 ) and GADD 45 . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Checkpoint effectors CDKN1A and Gadd 45 correlate with oxidative DNA damage in human prostate carcinoma . ^^^ MATERIALS AND METHODS : We examined the expression of CDKN1A and Gadd 45 proteins acting on cell cycle checkpoints and DNA repair in PCa relative to the presence of oxidative DNA damage , as measured by the detection of the DNA adduct 8 hydroxy 2 deoxyguanosine ( 8 OHdG . ) . ^^^ RT PCR was used to evaluate WAF 1 and Gadd 45 transcripts . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
However , cotreatment did not induce expression of other apoptosis related genes , p 21 ( WAF 1 ) and GADD 45 . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Many p 53 target genes , such as CDKN1A , GADD 45 , BTG 2 , and PLK 3 , were significantly up regulated at 2 hr post IR . ^^^ |
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Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
In the ML 1 human myeloid leukemia cell line , we have found that reducing the dose rate over three orders of magnitude results in some protection against the induction of apoptosis , but still causes linear induction of the p 53 regulated genes CDKN1A , GADD45A , and MDM 2 between 2 and 50 cGy . ^^^ Reducing the rate of exposure reduces the magnitude of induction of CDKN1A and GADD45A , but not the magnitude or duration of cell cycle delay . ^^^ One group of genes is induced in a dose rate dependent fashion , similar to GADD45A and CDKN1A . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Moreover , we found increased p 21 ( WAF 1 ) and gadd45A expression to be associated with the efficacy of the treatment ; this induction may correlate with activation of the IFN signalling pathway . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Gadd45a deletion allows another form of genomic instability , gene amplification , when p 21 ( Cdkn1a gene product ) is deleted also . ^^^ |
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Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Among candidate hypermethylated genes in cancer derived lines , there were eight ( CD 44 , CDKN1A , ESR 1 , PLAU , RARB , SFN , TNFRSF 6 , and TSPY ) previously observed in prostate cancer and 13 previously known methylation targets in other cancers ( ARHI , bcl 2 , BRCA 1 , CDKN2C , GADD45A , MTAP , PGR , SLC26A4 , SPARC , SYK , TJP 2 , UCHL 1 , and WIT 1 ) . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Consequently , UVB induced increase in the downstream effectors of p 53 , namely p21Cip1 and Gadd45a , were almost completely inhibited by NH2Cl . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
RESULTS : 5 FU treatment for 24 hours resulted in S phase arrests , p 53 accumulation , up regulation of p 53 target genes on DNA damage response ( ATF 3 , GADD 34 , GADD45A , PCNA ) , cell cycle regulatory ( CDKN1A ) , and apoptosis regulatory pathways ( FAS ) , and apoptosis induction in the parental and resistant cell lines . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
In addition to p15INK4b and p21CIP1 , these genes include mediators of stress responses ( GADD45A , GADD45B , and IER 1 ) and adaptive cell signaling responses ( CTGF , JAG 1 , LEMD 3 , SGK , CDC42EP3 , and OVOL 1 ) . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
Here , we determined that UVB induction of Gadd45a is necessary for G ( 2 ) arrest and that Gadd45a and its partner p 21 ( Waf 1 ) colocalize in nuclear bodies called Nuclear Speckles . ^^^ |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P24522 and P38936 |
Pubmed |
SVM Score :0.0 |
NA |
|