Journal of Biological Chemistry

Journal of Biological Chemistry

Volume 282, Issue 32, 10 August 2007, Pages 23572-23580
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Protein Synthesis, Post-Translational Modification, and Degradation
Spermidine/Spermine-N1-Acetyltransferase 2 Is an Essential Component of the Ubiquitin Ligase Complex That Regulates Hypoxia-inducible Factor 1α*

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Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that functions as a master regulator of oxygen homeostasis. The HIF-1α subunit is subjected to O2-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-N1-acetyltransferase (SSAT) 2 plays an essential role in this process. SSAT2 binds to HIF-1α, VHL, and Elongin C and promotes ubiquitination of hydroxylated HIF-1α 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-1α that is observed in oxygenated cells.

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This work was supported by Public Health Service Grant R01-HL55338 from the National Heart, Lung, and Blood Institute and by the Johns Hopkins Institute for Cell Engineering. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

© 2007 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.