COPing with hypoxia

Semin Cell Dev Biol. 2005 Aug-Oct;16(4-5):462-73. doi: 10.1016/j.semcdb.2005.03.002.

Abstract

To understand how cells respond to altered oxygenation, a frequent experimental paradigm is to isolate known components of bona fide oxygen responsive proteins. Recent studies have shown that a protein known as CSN5 or JAB1 interacts with both the HIF-1alpha oxygen-responsive transcription factor and its oxygen-dependent regulator, the Von Hippel-Lindau (pVHL) tumor suppressor. CSN5 is a component of the COP9 Signalosome (CSN) which is a multi-subunit protein that has high homology to the lid of the 19S lid of 26S proteasome. The exact function of the CSN5 interaction with pVHL and HIF-1alpha remains to be fully elucidated, but it is clear that the interaction is both oxygen dependent and that CSN5 may play different roles under oxic and hypoxic responses. Further, evidence has also been published indicating that pVHL can be potentially post-translationally modified by CSN5 (de-neddylation) and that CSN5 transcription is regulated by hypoxia as are many of the key pVHL/HIF-1alpha regulatory genes such as the PHDs and OS-9. This review will give a broad overview of known CSN5 and COP9 Signalosome functions and how these functions impact the pVHL/HIF-1alpha signaling complex and potentially other oxygen-sensitive response networks.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COP9 Signalosome Complex
  • Humans
  • Hypoxia / enzymology
  • Hypoxia / metabolism*
  • Molecular Sequence Data
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism*
  • Multiprotein Complexes / physiology
  • Oxidative Stress / physiology*
  • Peptide Hydrolases / chemistry
  • Peptide Hydrolases / metabolism*
  • Peptide Hydrolases / physiology
  • Signal Transduction / physiology*

Substances

  • Multiprotein Complexes
  • Peptide Hydrolases
  • COP9 Signalosome Complex