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KMID : 1140120060110040284
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Cancer Prevention Research
2006 Volume.11 No. 4 p.284 ~ p.290
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Decreased ARD1 Expression Stabilizes the HIF-1α Stability Under Hypoxia
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Jeong Joo-Won
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Abstract
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The stability and activity of HIF-1α are regulated by various post-translational modifications, hydroxylation, acetylation, and phosphorylation. Therefore, HIF-1α interacts with several protein factors including PHD, pVHL, ARD1, and p300/CBP. Under normoxia, the HIF-1α subunit is rapidly degraded via the von Hippel-Lindau tumor suppressor gene product (pVHL)-mediated ubiquitin-proteasome pathway. Mouse ARD1 has been reported to negatively regulate the hypoxia-inducible factor 1α (HIF-1α) protein by acetylating a lysine residue and enhancing HIF-1α ubiquitination and degradation. Herein,
it is demonstrated that ARD1 cannot affect the hydroxylation of HIF-1α, which is the major regulatory modification for the stability. Moreover, the ARD1 expression level is downregulated by hypoxic exposure.
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KEYWORD
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ARD1, HIF-1α, Hypoxia
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