title: CSN6 positively regulates c-Jun in a MEKK1-dependent manner.
abstract: c-Jun is a proto-oncoprotein that is commonly overexpressed in many types of cancer and is believed to regulate cell proliferation, the cell cycle, and apoptosis by controlling AP-1 activity. Understanding the c-Jun regulation is important to develop treatment strategy for cancer. The COP9 signalosome subunit 6 (CSN6) plays a critical role in ubiquitin-mediated protein degradation. MEKK1 is a serine/threonine kinase and E3 ligase containing PHD/RING domain involved in c-Jun ubiquitination. Here, we show that CSN6 associates with MEKK1 and reduces MEKK1 expression level by facilitating the ubiquitin-mediated degradation of MEKK1. Also we show that CSN6 overexpression diminishes MEKK1-mediated c-Jun ubiquitination, which is manifested in mitigating osmotic stress-mediated c-Jun downregulation. Thus, CSN6 is involved in positively regulating the stability of c-Jun. Overexpression of CSN6 correlates with the upregulation of c-Jun target gene expression in cancer. These findings provide new insight into CSN6-MEKK1-c-Jun axis in tumorigenesis.
authors.affiliation: a Departments of Molecular and Cellular Oncology ; The University of Texas MD Anderson Cancer Center ; Houston , TX USA.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Shin
authors.affiliation: a Departments of Molecular and Cellular Oncology ; The University of Texas MD Anderson Cancer Center ; Houston , TX USA.
authors.forename: Liem
authors.initials: L
authors.lastname: Phan
authors.affiliation: a Departments of Molecular and Cellular Oncology ; The University of Texas MD Anderson Cancer Center ; Houston , TX USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: b Molecular pathology; The University of Texas MD Anderson Cancer Center ; Houston , TX USA.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Lu
authors.affiliation: a Departments of Molecular and Cellular Oncology ; The University of Texas MD Anderson Cancer Center ; Houston , TX USA.
authors.forename: Mong-Hong
authors.initials: MH
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000075686:COP9 Signalosome Complex; D002460:Cell Line; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000235:genetics / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C470634:COPS6 protein, human; D016755:Proto-Oncogene Proteins c-jun; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; D000075686:COP9 Signalosome Complex
keywords: COP9 signalosome; CSN6; MEKK1; c-Jun