title: The COP9 signalosome and vascular function: intriguing possibilities?
abstract: Disorders of vascular function contribute importantly to cardiovascular disease which represents a substantial cause of morbidity and mortality worldwide. An emerging paradigm in the study of cardiovascular diseases is that protein ubiquitination and turnover represent key pathological mechanisms. Our understanding of these processes in the vasculature is growing but remains incomplete. Since protein ubiquitination and turnover can represent a terminal event in the life of a given protein, entry into these pathways must be highly regulated. However, at present understanding of these regulatory mechanisms, particularly in the vasculature, is fragmentary. The COP9 (constitutive photomorphogenic mutant 9) signalosome (CSN) is a heteromeric protein complex implicated in the control of protein degradation. The CSN participates critically in the control of Cullin Ring Ligases (CRLs), at least in part via the detachment of a small protein, Nedd8 (deneddylation). CRLs are one of the largest groups of ubiquitin ligases, which represent the most selective control point for protein ubiquitination. Thus, the CSN by virtue of its ability to control the CRLs ubiquitin ligase activity is ideally positioned to effect selective modulation of protein turnover. This review surveys currently available data regarding the potential role of the CSN in control of vascular function. Data potentially linking the CSN to control of regulatory proteins involved in vascular smooth muscle proliferation and to vascular smooth muscle contraction are presented with the intent of providing potentially intriguing possibilities for future investigation.
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota Vermillion, SD 57069, USA.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Martin
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota Vermillion, SD 57069, USA.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Wang
keywords: The COP9 signalosome; cullin-RING ligases; ubiquitination; vascular smooth muscle contraction; vascular smooth muscle proliferation