| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| N CoR also interacts with class 2 deacetylases HDAC 4 , HDAC 5 , and HDAC 7 . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| In contrast , SMRT does not activate the class 2 HDAC 4 , with which it also interacts . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| HDAC 9 is expressed in a tissue specific pattern that partially overlaps that of HDAC 4 . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| BRMS 1 interacted with class 2 HDACs , HDAC 4 , 5 , and 6 . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Among class 2 , there are five known members , namely HDAC 4 , HDAC 5 , HDAC 6 , HDAC 7 and HDAC 9 . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Data from protease protection assays with GAT 1 prolactin chimeras has shown that residues in the loops connecting hydrophobic domain ( HD ) 3 and HD 4 and HD 7 and HD 8 are accessible to protease in the cytoplasm and suggest the presence of pore loop structures which extend into the membrane from the extracellular face . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| PATIENTS AND METHODS : This analysis comprises 4 , 626 HL patients of all prognostic risk groups who were enrolled onto the multicenter studies HD 4 to HD 9 of the German Hodgkin Study Group . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| The corresponding full length cDNAs were cloned and defined as HDAC 4 , HDAC 5 , and HDAC 6 . ^^^ However , HDAC 4 and HDAC 5 associate with HDAC 3 in vivo . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Here we show that these RDs are nonredundant , and that one RD , which is conserved in N CoR and SMRT , represses transcription by interacting directly with class 2 HDAC 4 and HDAC 5 . ^^^ Endogenous N CoR and SMRT each associate with HDAC 4 in a complex that does not contain mSin3A or HDAC 1 . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| To date , six HDACs have been identified in mammalian cells : the yeast RPD 3 homologs HDAC 1 , 2 , and 3 and the yeast HDA 1 homologs HDAC 4 , 5 , and 6 . ^^^ HDAC 4 and HDAC 5 contain a noncatalytic N terminal domain . ^^^ Herein , we report the identification of a protein HDRP ( HDAC related protein ) that shares 50 % identity in deduced amino acid sequence to the noncatalytic N terminal domain of HDAC 4 and 5 . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| To characterize the cellular function of the recently identified HDAC 4 and HDAC 5 proteins , complexes were isolated by immunoprecipitation . ^^^ The association of 14 3 3 with HDAC 4 and HDAC 5 results in the sequestration of these proteins in the cytoplasm . ^^^ Loss of this interaction allows HDAC 4 and HDAC 5 to translocate to the nucleus , interact with HDAC 3 , and repress gene expression . ^^^ Regulation of the cellular localization of HDAC 4 and HDAC 5 by 14 3 3 represents a mechanism for controlling the transcriptional activity of these class 2 HDAC proteins . . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| To further define the mechanisms that confer CaMK responsiveness to HDAC 4 and 5 , we performed yeast two hybrid screens to identify HDAC interacting factors . ^^^ These screens revealed interactions between HDAC 4 and members of the 14 3 3 family of proteins , which function as signal dependent intracellular chaperones . ^^^ HDAC 4 binds constitutively to 14 3 3 in yeast and mammalian cells , whereas HDAC 5 binding to 14 3 3 is largely dependent on CaMK signaling . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Interestingly , HDAC 6 , but not HDAC 1 or HDAC 4 , was resistant to TPX and CHAP 1 , whereas TSA inhibited these HDACs to a similar extent . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| SMRTE inhibits MEF2C transcriptional activation by targeting HDAC 4 and 5 to nuclear domains . ^^^ Intriguingly , although HDAC 4 is located primarily in the cytoplasm , coexpression of SMRTe dramatically translocates HDAC 4 from the cytoplasm into the nucleus , where HDAC 4 prevents MEF2C from activating muscle differentiation . ^^^ Accordingly , SMRTe synergizes with HDAC 4 and 5 to inhibit MEF2C transactivation of target promoter , suggesting that nuclear domain targeting of HDAC4 / 5 may be important in preventing muscle cell differentiation . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| The ability of HDAC 4 and 5 to inhibit MEF 2 is blocked by phosphorylation of these HDACs at two conserved serine residues , which creates docking sites for the intracellular chaperone protein 14 3 3 . ^^^ MEF 2 interacting transcription repressor ( MITR ) shares homology with the amino terminal regions of HDAC 4 and 5 , but lacks an HDAC catalytic domain . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Different class 2 HDACs reside in the cell nucleus in stable and autonomous complexes with enzymatic activity , but the enzymatic activities associated with HDAC 7 and HDAC 4 rely on shared cofactors , including HDAC 3 and SMRT / N CoR . . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Here we show that HDAC 4 and 5 each contain a signal responsive nuclear export sequence ( NES ) at their extreme carboxy termini . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Furthermore , GATA 2 also directly associated with HDAC 5 but not with other class 2 HDACs examined , that is , HDAC 4 and HDAC 6 . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Interestingly , HDAC 6 , but not HDAC 1 or HDAC 4 , was resistant to TPX and CHAP 1 , while TSA inhibited these HDACs to a similar degree . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Moreover , class 1 HDACs ( HDAC 1 and 3 ) , not class 2 HDACs ( HDAC 4 , 5 , and 6 ) , were co immunoprecipitated with Smad 6 . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Here , we show that the catalytic domain of HDAC 4 interacts with HDAC 3 via the transcriptional corepressor N CoR / SMRT . ^^^ All experimental conditions leading to the suppression of HDAC 4 binding to SMRT / N CoR and to HDAC 3 result in the loss of enzymatic activity associated with HDAC 4 . ^^^ In vitro reconstitution experiments indicate that HDAC 4 and other class 2 HDACs are inactive in the context of the SMRT / N CoR HDAC 3 complex and do not contribute to its enzymatic activity . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| HDAC 1 and HDAC 2 were more strongly inhibited by redFK than HDAC 4 and HDAC 6 . redFK was less active than FK 228 in inhibiting in vivo HDAC activity , due to rapid inactivation in medium and serum . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| The intracellular fate of HDAC 4 was followed by transfection of smooth muscle cells with an HDAC 4 Green Fluorescent Protein fusion hybrid . ^^^ The 14 3 3beta double mutant prevented HDAC 4 cytoplasmic localization in the presence of active CaM kinase 1 or 4 . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| HDAC 4 foci gradually disappeared in repair proficient cells but persisted in repair deficient cell lines or cells irradiated with a lethal dose , suggesting that resolution of HDAC 4 foci is linked to repair . ^^^ Silencing of HDAC 4 via RNA interference surprisingly also decreased levels of 53BP1 protein , abrogated the DNA damage induced G 2 delay , and radiosensitized HeLa cells . ^^^ Our combined results suggest that HDAC 4 is a critical component of the DNA damage response pathway that acts through 53BP1 and perhaps contributes in maintaining the G 2 cell cycle checkpoint . . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Functional characterization of an amino terminal region of HDAC 4 that possesses MEF 2 binding and transcriptional repressive activity . ^^^ The amino terminus of HDAC 4 can associate with the DNA bound MEF 2 in vitro , suggesting that it does not repress MEF 2 simply by disrupting the ability of MEF 2 to bind DNA . ^^^ In vivo , MEF 2 induces nuclear translocation of both the full length HDAC 4 and HDAC 4 ( 1 208 ) , whereas the nuclear HDAC 4 as well as HDAC 4 ( 1 208 ) in turn specifically sequesters MEF 2 to distinct nuclear bodies . ^^^ In addition , we show that MyoD and HDAC 4 functionally antagonize each other to regulate MEF 2 activity . ^^^ Combined with data from others , our data suggest that the full length HDAC 4 can repress MEF 2 through multiple independent repressive domains . . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Interestingly , the upregulated HDACs all belong to class 2 of histone deacetylases . mRNAs for HDAC 4 , 8 and 10 were not detectable by Northern analysis . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| SiRNA for HDAC 4 or 7 produced no morphological changes in HeLa S 3 cells . ^^^ HDAC 1 and 3 siRNA produced a concentration dependent inhibition of HeLa cell proliferation ; whereas , HDAC 4 and 7 siRNA showed no effect . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| In the present study , we investigated whether class 1 and class 2 HDACs interact with GATA 1 to regulate its function and indeed , GATA 1 is directly associated with HDAC 3 , HDAC 4 and HDAC 5 . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| In vitro biochemical studies showed that recombinant HDAC 6 , but not HDAC 4 , bound directly to the protein phosphatase ( PP ) 1 catalytic subunit . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Here , we demonstrate that caspases can repress the activity of the myocyte enhancer factor ( MEF ) 2C transcription factor by regulating HDAC 4 processing . ^^^ Cleavage of HDAC 4 occurs at Asp 289 and disjoins the carboxy terminal fragment , localized into the cytoplasm , from the amino terminal fragment , which accumulates into the nucleus . ^^^ In the nucleus , the caspase generated fragment of HDAC 4 is able to trigger cytochrome c release from mitochondria and cell death in a caspase 9 dependent manner . ^^^ The caspase cleaved amino terminal fragment of HDAC 4 acts as a strong repressor of the transcription factor MEF2C , independently from the HDAC domain . ^^^ Removal of amino acids 166 289 from the caspase cleaved fragment of HDAC 4 abrogates its ability to repress MEF 2 transcription and to induce cell death . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Histone deacetylase 4 ( HDAC 4 ) is a class 2 HDAC implicated in controlling gene expression important for diverse cellular functions , but little is known about how its expression and stability are regulated . ^^^ Histone deacetylase 4 ( HDAC 4 ) is a class 2 HDAC implicated in controlling gene expression important for diverse cellular functions , but little is known about how its expression and stability are regulated . ^^^ Consistent with the instability of HDAC 4 protein , its mRNA was also highly unstable ( with a half life of less than 4 h ) . ^^^ The degradation of HDAC 4 could be accelerated by exposure of cells to ultraviolet irradiation . ^^^ HDAC 4 degradation was not dependent on proteasome or CRM 1 mediated export activity but instead was caspase dependent and was detectable in diverse human cancer lines . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| In both Neuro 2a and N 9 cells the highest increase was observed for HDAC 5 and 6 mRNA , whereas , HDAC 4 had a prominent increase in mRNA levels after drug treatment only in N 9 microglia cell line but not in Neuro 2a . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Following DNA damage , p 53 is rapidly acetylated at K 320 and K 373 to K 382 , histones are deacetylated , and the release of PCAF and p 300 correlates with the recruitment of histone deacetylases ( HDACs ) HDAC 1 before HDAC 4 and HDAC 5 and promoter repression . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| When tested against human HDAC 1 and HDAC 4 , 2f showed no inhibitory activity against HDAC 1 but was able to inhibit HDAC 4 . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Accordingly , HDAC 4 or 5 is required for efficient TGF beta mediated inhibition of Runx 2 function and is involved in osteoblast differentiation . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| To understand the physiological functions of HDACs , we characterized six different Drosophila HDACs , including Rpd 3 , HDAC 3 , HDAC 4 , HDAC 6 S , HDAC 6 L , and Sir 2 , by developmental expression pattern , transcriptional profiles of target genes , and sensitivity to HDAC inhibitors . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| The HDAC inhibitor , trichostatin A , reduced MMSET 1 repression activity and in vitro co immunoprecipitation analyses indicated that MMSET 1 specifically recruits HDAC 1 and mSin3b , but not HDAC 2 or HDAC 4 . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Histone deacetylase 4 ( HDAC 4 ) undergoes signal dependent shuttling between the cytoplasm and nucleus , which is regulated in part by calcium / calmodulin dependent kinase ( CaMK ) mediated phosphorylation . ^^^ Histone deacetylase 4 ( HDAC 4 ) undergoes signal dependent shuttling between the cytoplasm and nucleus , which is regulated in part by calcium / calmodulin dependent kinase ( CaMK ) mediated phosphorylation . ^^^ Here , we report that HDAC 4 intracellular trafficking is important in regulating neuronal cell death . ^^^ HDAC 4 is normally localized to the cytoplasm in brain tissue and cultured cerebellar granule neurons ( CGNs ) . ^^^ However , in response to low potassium or excitotoxic glutamate conditions that induce neuronal cell death , HDAC 4 rapidly translocates into the nucleus of cultured CGNs . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Histone deacetylases mediate critical cellular functions but relatively little is known about mechanisms controlling their expression , including expression of HDAC 4 , a class 2 HDAC implicated in the modulation of cellular differentiation and viability . ^^^ Endogenous HDAC 4 mRNA , protein levels and promoter activity were all readily repressed by mithramycin , suggesting regulation by GC rich DNA sequences . ^^^ We validated consensus binding sites for Sp1 / Sp3 transcription factors in the HDAC 4 promoter through truncation studies and targeted mutagenesis . ^^^ Cotransfection of either Sp 1 or Sp 3 with a reporter driven by the HDAC 4 promoter led to high activities in SL 2 insect cells ( which lack endogenous Sp1 / Sp3 ) . ^^^ In human cells , restored expression of Sp 1 and Sp 3 up regulated HDAC 4 protein levels , whereas levels were decreased by RNA interference mediated knockdown of either protein . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Genetic analysis has revealed that Runx 2 is degraded through a Smurf mediated ubiquitination pathway , and its activity is inhibited by HDAC 4 . ^^^ HDAC 4 and HDAC 5 dea cetylate Runx 2 , allowing the protein to undergo Smurf mediated degradation . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Here we show that calcium / calmodulin dependent kinase 2 ( CaMKII ) signals specifically to HDAC 4 by binding to a unique docking site that is absent in other class IIa HDACs . ^^^ Phosphorylation of HDAC 4 by CaMKII promotes nuclear export and prevents nuclear import of HDAC 4 , with consequent derepression of HDAC target genes . ^^^ In cardiomyocytes , CaMKII phosphorylation of HDAC 4 results in hypertrophic growth , which can be blocked by a signal resistant HDAC 4 mutant . ^^^ These findings reveal a central role for HDAC 4 in CaMKII signaling pathways and have implications for the control of gene expression by calcium signaling in a variety of cell types . . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| LPS transiently repressed , then induced a number of HDACs ( Hdac 4 , 5 , 7 ) in BMM , whereas Hdac 1 mRNA was induced more rapidly . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Class 2 members , including HDAC 4 , HDAC 5 , HDAC 6 , HDAC 7 , and HDAC 9 , possess domains similar to the deacetylase domain of yeast Hdal . ^^^ HDAC 4 , HDAC 5 , and HDAC 7 function as transcriptional corepressors that interact with the MEF 2 transcription factors and the N CoR , BCoR , and CtBP corepressors . ^^^ Intriguingly , HDAC 4 , HDAC 5 , and probably HDAC 7 are regulated through subcellular compartmentalization controlled by site specific phosphorylation and binding of 14 3 3 proteins ; the regulation of these HDACs is thus directly linked to cellular signaling networks . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Our results indicate that three related class 2 deacetylases , HDAC 4 , HDAC 5 , and HDAC 7 can associate with BCL 6 in vivo and in vitro . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Within class 2 , HDAC 4 , HDAC 5 , HDAC 7 , and HDAC 9 share similar domain organization both within the N terminal extension and the C terminal catalytic domain , thus forming a subclass known as class IIa . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| MEF 2 has been reported to be associated with several distinct repressors including Cabin 1 ( cain ) , MEF 2 interacting transcriptional repressor ( MITR ) , and HDAC 4 . ^^^ However , it was not known whether the binding of HDAC 4 and MITR to MEF 2 is also regulated by calcium . ^^^ We report that HDAC 4 and MITR contain calmodulin binding domains that overlap with their MEF 2 binding domains . ^^^ Together , HDAC 4 , MITR , and Cabin 1 constitute a family of calcium sensitive transcriptional repressors of MEF2 . . ^^^ |
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| Interacting proteins: Q9UKV0 and P56524 |
Pubmed |
SVM Score :0.0 |
| Here we report that MITR , HDAC 4 , and HDAC 5 associate with heterochromatin protein 1 ( HP 1 ) , an adaptor protein that recognizes methylated lysines within histone tails and mediates transcriptional repression by recruiting histone methyltransferase . ^^^ |
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