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.
Highlights
Through detailed knowledge of oncogenic signal transduction pathways, targeted therapies have provided exciting advancements in the treatment of cancer where standard chemotherapy alone has failed
The exact role that Jun activation domain-binding protein-1 (Jab1)/CSN subunit 5 (CSN5) plays in oncogenic processes and which of its many functions contributes to these processes is far from being fully understood
It would be interesting to determine whether Jab1/CSN5 contributes to tumorigenesis through one specific interaction or the accumulation of multiple interactions
Summary
Through detailed knowledge of oncogenic signal transduction pathways, targeted therapies have provided exciting advancements in the treatment of cancer where standard chemotherapy alone has failed. Jab1/CSN5 was originally identified as a c-Jun coactivator and subsequently discovered to be the fifth member and an integral component of the constitutive photomorphogenic-9 (COP9) signalosome (CSN) complex, a multifunctional protein complex involved in modulating signal transduction, gene transcription, and protein stability in cells [1,2,3]. Jab1/CSN5 plays an essential role in positively regulating cellular proliferation by functionally inactivating several key negative regulatory proteins and tumor suppressors through their subcellular localization, degradation, and deneddylation, including p53, Smad 4/7, and the cyclin-dependent kinase inhibitor p27Kip (p27) [5,6,7,8] It is capable of stabilizing certain proteins, including hypoxia-inducible factor 1a (HIF-1a) and cJun, as well as acting as a transcriptional co-factor for MYC, which is responsible for the transcriptional activation of genes involved in cell proliferation, angiogenesis, and invasion [1,9,10]. Regulation of Jab1/CSN5’s activity One of the potentially oncogenic mechanisms of JAB1/ CSN5 overexpression is through gene amplification by
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
