The COP9/signalosome increases the efficiency of von Hippel-Lindau protein ubiquitin ligase-mediated hypoxia-inducible factor-alpha ubiquitination

The Journal of Biological Chemistry
Yasuhiro MiyauchiKazuhiro Iwai

Abstract

Oxygen-dependent ubiquitination of the alpha-subunit of hypoxia-inducible factor (HIF-alpha) by the (von Hippel-Lindau protein)-Elongin B/C-Cullin2-Rbx1 (VBC-Cul2) ubiquitin ligase, a member of the cullin-RING ubiquitin ligases (CRLs), plays a central role in controlling oxygen metabolism. Nedd8 conjugation of cullins enhances the ligase activity of CRLs, and the COP9/signalosome (CSN) enhances the degradation of several CRL substrates, although it removes Nedd8 from cullins. Here we demonstrate that CSN increased the efficiency of the VBC-Cul2 complex for recognizing and ubiquitinating substrates by facilitating the dissociation of ubiquitinated substrates from the pVHL subunit of the complex. Moreover CSN enhanced HIF-1alpha degradation by promoting the dissociation of HIF-1alpha from pVHL in cells. The length of the polyubiquitin chain conjugated to the substrate appeared to be involved in CSN-mediated dissociation of the substrate from pVHL. In contrast to other mechanisms underlying CSN-mediated activation of CRLs, the dissociation of ubiquitinated substrates from pVHL did not require the deneddylation activity of CSN, implying that CSN enhances degradation of CRL substrates by multiple mechanisms.

References

May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·D LiakopoulosA Pause
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·K IwaiA Pause
Dec 28, 1999·Annual Review of Cell and Developmental Biology·G L Semenza
May 5, 2001·Science·S LyapinaR J Deshaies
Aug 3, 2001·The EMBO Journal·T KawakamiK Tanaka
Oct 13, 2001·Science·R K Bruick, S L McKnight
Nov 15, 2001·The Journal of Biological Chemistry·Moon-Kyoung BaeKyu-Won Kim
Mar 28, 2002·Physiological Reviews·Michael H Glickman, Aaron Ciechanover
Feb 8, 2003·Current Opinion in Genetics & Development·William Kim, William G Kaelin
Aug 2, 2003·The New England Journal of Medicine·Daniel J George, William G Kaelin
Apr 15, 2004·Genes & Development·Lynne BemisWayne Zundel
Feb 3, 2005·Nature Reviews. Molecular Cell Biology·Matthew D Petroski, Raymond J Deshaies
Jun 22, 2005·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yuzuru MegumiKazuhiro Iwai
Aug 30, 2005·Nature Cell Biology·June-Tai WuCheng-Ting Chien
Feb 2, 2006·Molecular and Cellular Biology·Shih-Ching Lo, Mark Hannink
Feb 24, 2007·The EMBO Journal·Katrin SchweitzerMichael Naumann
Apr 19, 2007·The Journal of Biological Chemistry·Eng-Hui Chew, Thilo Hagen

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