| Interacting proteins: P41227 and Q16665 |
Pubmed |
SVM Score :0.0 |
| Regulation and destabilization of HIF 1alpha by ARD 1 mediated acetylation . ^^^ In this report , we reveal an important function for ARD 1 in mammalian cells as a protein acetyltransferase by direct binding to HIF 1alpha to regulate its stability . ^^^ We present further evidence showing that ARD 1 mediated acetylation enhances interaction of HIF 1alpha with pVHL and HIF 1alpha ubiquitination , suggesting that the acetylation of HIF 1alpha by ARD 1 is critical to proteasomal degradation . ^^^ Therefore , we have concluded that the role of ARD 1 in the acetylation of HIF 1alpha provides a key regulatory mechanism underlying HIF 1alpha stability . . ^^^ |
|
| Interacting proteins: P41227 and Q16665 |
Pubmed |
SVM Score :0.0 |
| ARD 1 acetylates HIF 1alpha and stimulates pVHL mediated ubiquitination of HIF 1alpha . ^^^ |
|
| Interacting proteins: P41227 and Q16665 |
Pubmed |
SVM Score :0.0 |
| In addition to the HIF proline hydroxylases and asparagine hydroxylases , ARD 1 is recently described as a HIF 1alpha acetylase that regulates its stability . ^^^ |
|
| Interacting proteins: P41227 and Q16665 |
Pubmed |
SVM Score :0.0 |
| Among the multiple reported modifications , acetylation , by an acetyltransferase termed arrest defective 1 protein ( ARD 1 ) , has been reported to decrease HIF 1alpha stability and therefore impact on hypoxic gene expression . ^^^ In contrast , we report that both overexpression and silencing of ARD 1 had no impact on the stability of HIF 1alpha or 2alpha and that cells silenced for ARD 1 maintained hypoxic nuclear localization of HIF 1alpha . ^^^ Using two model systems ( ( a ) wild type and HIF 1alpha null mouse embryo fibroblasts and ( b ) HeLa cells silenced for HIF 1alpha or 2alpha by RNA interference ) , we demonstrate that the level of expression of the ARD 1 protein is independent of HIF 1alpha and 2alpha . ^^^ |
|
| Interacting proteins: P41227 and Q16665 |
Pubmed |
SVM Score :0.0 |
| ARD 1 has also been implicated in the destabilization of the transcription factor HIF 1alpha ( hypoxia inducible factor 1alpha ) . ^^^ |
|
| Interacting proteins: P41227 and Q16665 |
Pubmed |
SVM Score :0.0 |
| It was suggested that mammalian ARD 1 acetylates HIF 1 alpha and thereby enhances HIF 1 alpha ubiquitination and degradation . ^^^ Furthermore , ARD 1 was proposed to be down regulated in hypoxia thus facilitating the stabilization of HIF 1 alpha . ^^^ |
|
| Interacting proteins: P41227 and Q16665 |
Pubmed |
SVM Score :0.0 |
| Mouse ARD 1 ( mARD 1 ) has been reported to negatively regulate the hypoxia inducible factor 1alpha ( HIF 1alpha ) protein by acetylating a lysine residue and enhancing HIF 1alpha ubiquitination and degradation . ^^^ However , it was recently reported that human ARD 1 ( hARD 1 ) does not affect HIF 1alpha stability . ^^^ The effects of ARD 1 variants were evaluated with respect to HIF 1alpha stability and acetylation activity . ^^^ These results suggest that ARD 1 variants might have different effects on HIF 1alpha stability and acetylation , which may reflect diverse biological functions that remain to be determined . . ^^^ |
|
| Interacting proteins: P41227 and Q16665 |
Pubmed |
SVM Score :0.0 |
| The stability and / or activity of human HIF 1alpha are modulated by post translational modifications including prolyl and asparaginyl hydroxylation , phosphorylation , and reportedly by acetylation of the side chain of Lys 532 by ARD 1 ( arrest defective protein 1 homologue ) , an acetyltransferase . ^^^ Using purified recombinant human ARD 1 ( hARD 1 ) we did not observe ARD 1 mediated N acetylation of Lys 532 using fragments of HIF 1alpha . ^^^ |
|
| Interacting proteins: P41227 and Q16665 |
Pubmed |
SVM Score :0.0 |
| MTA 1 counteracted to the action of acetyltransferase , ARD 1 , and it did not stabilize the HIF 1alpha mutant that lacks the acetylation site , K532R . ^^^ |
|
| Interacting proteins: P41227 and Q16665 |
Pubmed |
SVM Score :0.0 |
| ARD 1 , the acetyltransferase , acetylates HIF 1a at lysine 532 , which enhances the interaction of HIF 1a with pVHL . ^^^ Therefore , FIH 1 and ARD 1 negatively regulate the transcriptional activity and the stability of HIF 1a . ^^^ |
|
| Interacting proteins: P41227 and Q16665 |
Pubmed |
SVM Score :0.0 |
| Cells were transiently transfected with HIF 1alpha mutant and antisense arrest defective 1 protein ( ARD 1 ) , and HIF 1alpha acetylation was assayed by immunoprecipitation . ^^^ Transfection with antisense ARD 1 decreased the level of acetylated HIF 1alpha and restored HIF 1alpha and VEGF A expression in CTGF overexpressing cells . ^^^ |
|
| Interacting proteins: P41227 and Q16665 |
Pubmed |
SVM Score :0.0 |
| Expression of HIF 1alpha and VEGF was examined in two oesophageal squamous cell carcinoma cell lines ( TE 2 , TE 3 ) and 82 archival surgical specimens of human oesophageal squamous cell carcinoma tissue . ^^^ |
|
| Interacting proteins: P41227 and Q16665 |
Pubmed |
SVM Score :0.0 |
| NA |
|