NF-κB1 inhibits c-Myc protein degradation through suppression of FBW7 expression.

摘要: // Haishan Huang 1,2 , Li Ma 2 Jingxia Yonghui Yu Dongyun Zhang Jinlong Wei Honglei Jin Derek Xu 2,3 Jimin Gao 1 and Chuanshu Zhejiang Provincial Key Laboratory for Technology & Application of Model Organisms, School Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China Nelson Institute Environmental Medicine, New York University Tuxedo, NY, USA 3 Jericho High School, Jericho, NY Correspondence: Huang, email: Gao, Keywords : NF-κB p50, arsenite, c-Myc, protein degradation, FBW7 Received November 29, 2013 Accepted January 15, 2014 Published Abstract is a well-known transcription factor in regulation multiple gene biological processes, most them are relied on its transcriptional activity the p65/RelA subunit, while function another ubiquitously expressed subunit NF-κB1 (p50) remains largely unknown due to lack activation domain. Here we discovered novel p50 as regulator oncogenic c-Myc degradation upon arsenite treatment transcriptional-independent mechanism. Our results found that was crucial induction following by using specific knockdown deletion normal cells well reconstituting expression deficient cells. Subsequently showed upregulated mainly through inhibiting degradation. We also identified exhibited this property suppression expression. profoundly p50-defecient comparison intact cells, whereas p50-/- restored arsenite-induced accumulation, assuring up-regulation responsible defect In addition, suppressed fbw7 via E2F1 transactivation. Collectively, our studies demonstrated contributing notion p50-regulated levels at translation further providing significant insight into understanding biomedical significance protein.