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Open Access Highly Accessed Review

JAB1/CSN5: a new player in cell cycle control and cancer

Terry J Shackleford and Francois X Claret*

Author Affiliations

Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA

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Cell Division 2010, 5:26  doi:10.1186/1747-1028-5-26

Published: 18 October 2010

Abstract

c-Jun activation domain-binding protein-1 (Jab1) acts as a modulator of intracellular signaling and affects cellular proliferation and apoptosis, through its existence as a monomer or as the fifth component of the constitutive photomorphogenic-9 signalosome (CSN5). Jab1/CSN5 is involved in transcription factor specificity, deneddylation of NEDD8, and nuclear-to-cytoplasmic shuttling of key molecules. Jab1/CSN5 activities positively and negatively affect a number of pathways, including integrin signaling, cell cycle control, and apoptosis. Also, more recent studies have demonstrated the intriguing roles of Jab1/CSN5 in regulating genomic instability and DNA repair. The effects of Jab1/CSN5's multiple protein interactions are generally oncogenic in nature, and overexpression of Jab1/CSN5 in cancer provides evidence that it is involved in the tumorigenic process. In this review, we highlight our current knowledge of Jab1/CSN5 function and the recent discoveries in dissecting the Jab1 signaling pathway. Further, we also discuss the regulation of Jab1/CSN5 in cancers and its potential as a therapeutic target.