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Spermidine/spermine-N1-acetyltransferase 2 is an essential component of the ubiquitin ligase complex that regulates hypoxia-inducible factor 1α

被引：48
作者：
Baek, Jin Hyen
Liu, Ye V.
McDonald, Karin R.
Wesley, Jacob B.
Hubbi, Maimon E.
Byun, Hweejo
Semenza, Gregg L.
机构：
[1] Johns Hopkins Univ, Sch Med, Vasc Biol Program, Inst Cell Engn,Dept Pediat, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Vasc Biol Program, Inst Cell Engn,Dept Med, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Vasc Biol Program, Inst Cell Engn,Dept Oncol, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Sch Med, Vasc Biol Program, Inst Cell Engn,Dept Radiat Oncol, Baltimore, MD 21205 USA
[5] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA
来源：
JOURNAL OF BIOLOGICAL CHEMISTRY | 2007年 / 282卷 / 32期
关键词：
D O I：
10.1074/jbc.M703504200
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要：
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that functions as a master regulator of oxygen homeostasis. The HIF-1 subunit is subjected to O-2-dependent prolyl hydroxylation leading to ubiquitination by the von Hippel-Lindau protein (VHL)-Elongin C ubiquitin-ligase complex and degradation by the 26 S proteasome. In this study, we demonstrate that spermidine/spermine-N-1-acetyltransferase (SSAT) 2 plays an essential role in this process. SSAT2 binds to HIF-1 alpha, VHL, and Elongin C and promotes ubiquitination of hydroxylated HIF-1 alpha by stabilizing the interaction of VHL and Elongin C. Multivalent interactions by SSAT2 provide a mechanism to ensure efficient complex formation, which is necessary for the extremely rapid ubiquitination and degradation of HIF-1 alpha that is observed in oxygenated cells.
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收藏
页码：23572 / 23580
页数：9
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