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The emerging role of the COP9 signalosome in cancer.

Abstract
In the last several years, multiple lines of evidence have suggested that the COP9 signalosome (CSN) plays a significant role in the regulation of multiple cancers and could be an attractive target for therapeutic intervention. First, the CSN plays a key role in the regulation of Cullin-containing ubiquitin E3 ligases that are central mediators of a variety of cellular functions essential during cancer progression. Second, several studies suggest that the individual subunits of the CSN, particularly CSN5, might regulate oncogenic and tumor suppressive functions independently of, or coordinately with, the CSN holocomplex. Thus, deregulation of CSN subunit function can have a dramatic effect on diverse cellular functions, including the maintenance of DNA fidelity, cell cycle control, DNA repair, angiogenesis, and microenvironmental homeostasis that are critical for tumor development. Additionally, clinical studies have suggested that the expression or localization of some CSN subunits correlate to disease progression or clinical outcome in a variety of tumor types. Although the study of CSN function in relation to tumor progression is in its infancy, this review will address current studies in relation to cancer initiation, progression, and potential for therapeutic intervention.
AuthorsKatharine S Richardson, Wayne Zundel
JournalMolecular cancer research : MCR (Mol Cancer Res) Vol. 3 Issue 12 Pg. 645-53 (Dec 2005) ISSN: 1541-7786 [Print] United States
PMID16380502 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Cullin Proteins
  • Multiprotein Complexes
  • Peptide Hydrolases
  • COP9 Signalosome Complex
Topics
  • Animals
  • COP9 Signalosome Complex
  • Cell Cycle
  • Cullin Proteins (metabolism)
  • DNA Damage
  • DNA Repair
  • Humans
  • Multiprotein Complexes (physiology)
  • Neoplasms (blood supply, metabolism, pathology)
  • Neovascularization, Pathologic (metabolism)
  • Peptide Hydrolases (physiology)
  • Signal Transduction

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