Role of CSN5/JAB1 in Wnt/尾-catenin activation in colorectal cancer cells

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• 作者：Anke K. Schü ; tz ; Thomas Hennes ; Sandra Jumpertz ; Simone Fuchs ; Jü ; rgen Bernhagen ; ^{jbernhagen@ukaachen.de}
• 关键词：CSN5 ; COP9 signalosome ; Protein degradation ; Cullin-RING-ubiquitin ligase ; MIF ; p53
• 刊名：FEBS Letters
• 出版年：2012
• 期刊代码：70_00145793
• 类别：bio
• 出版时间：4 June, 2012
• 卷：586
• 期：11
• 页码：1645-1651
• 文件大小：451 K

摘要

CSN5/JAB1 is a critical subunit of the COP9 signalosome (CSN) and is overexpressed in many human cancers, but little is known about the role of CSN5 in colorectal cancer (CRC). To explore the functional role of CSN5 in colorectal tumorigenesis, we applied siRNA technology to silence CSN5 in HeLa, SW480, HCT116, HT29, and CaCo2 cells. CSN5 knock-down led to reduced 尾-catenin and phospho-尾-catenin levels and this was paralleled by reduced CRC cell proliferation and reduced apoptosis rates, whereas the short-term 尾-catenin protein stability was enhanced by CSN5 knock-down in SW480 cells. Together, these data implicate the CSN in the pathogenesis of CRC via regulation of the Wnt/尾-catenin pathway.