Regulation and destabilization of HIF-1α by ARD1-mediated acetylation

Joo Won Jeong, Moon Kyoung Bae, Mee Young Ahn, Se Hee Kim, Tae Kwon Sohn, Myung Ho Bae, Mi Ae Yoo, Eun Joo Song, Kong Joo Lee, Kyu Won Kim

Research output: Contribution to journalArticlepeer-review

593 Scopus citations

Abstract

Hypoxia-inducible factor 1 (HIF-1) plays a central role in cellular adaptation to changes in oxygen availability. Recently, prolyl hydroxylation was identified as a key regulatory event that targets the HIF-1α subunit for proteasomal degradation via the pVHL ubiquitination complex. In this report, we reveal an important function for ARD1 in mammalian cells as a protein acetyltransferase by direct binding to HIF-1α to regulate its stability. We present further evidence showing that ARD1-mediated acetylation enhances interaction of HIF-1α with pVHL and HIF-1α ubiquitination, suggesting that the acetylation of HIF-1α by ARD1 is critical to proteasomal degradation. Therefore, we have concluded that the role of ARD1 in the acetylation of HIF-1α provides a key regulatory mechanism underlying HIF-1α stability.

Original languageEnglish
Pages (from-to)709-720
Number of pages12
JournalCell
Volume111
Issue number5
DOIs
StatePublished - 27 Nov 2002

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