The emerging role of the COP9 signalosome in cancer.
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.
Richardson
Katharine S
KS
Department of Pharmacology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Zundel
Wayne
W
D000818:Animals; D000075686:COP9 Signalosome Complex; D002453:Cell Cycle; D044842:Cullin Proteins / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D046912:Multiprotein Complexes / Q000502:physiology*; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010447:Peptide Hydrolases / Q000502:physiology*; D015398:Signal Transduction
D044842:Cullin Proteins; D046912:Multiprotein Complexes; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex