β-arrestin 2通过结合RIP1抑制TNFα诱导的IKKα/β活化
β-arrestin 2 inhibits TNFα induced IKKα/β activation by interacting with RIP1
沈江 1戚灶明 1王坚2
作者信息
- 1. 诸暨市人民医院普外科,浙江诸暨311800
- 2. 浙江大学医学院附属第二医院普外科,浙江杭州310009
- 折叠
摘要
目的:探讨β-arrestin 2对肿瘤坏死因子α(TNFα)信号转导的调控作用.方法:在HT-29细胞过表达β-arrestin 2和下扰β-arrestin 2表达后,用TNFα刺激相应时间点,用免疫共沉淀和Western印迹法观察TNFα诱导的下游信号转导分子IKKα/β(I-kappa-B kinase α/β),IkBα,TAK1(TGF-beta activated kinase 1),JNK(c-jun N.terminal kinase),p38的活化及可能机制.结果:β-arrestin 2通过结合RIP1并抑制TNFα诱导的RIP1的多聚泛素化,抑制TNFα诱导的IKKα/β及下游信号通路活化,TAK1及其下游信号通路则活化增强.干扰β-arrestin 2表达从反向说明β-arrestin 2对TNFα的信号转导调控.结论:β-arrestin 2通过结合并抑制RIP1多聚泛素化抑制TNFα诱导的IKKα/β活化,而促进TAK1活化.
Abstract
AIM:To investigate the effects of β-arrestin 2 on TNFα signal transduction.METHODS:β-arrestin 2 was overexpressed or knockdowned in HT-29 cells,and HT-29 cells were stimulated with different time period,signal transduction ofIKKα/β.IkBα TAKl JNK p38 and the potential mechnism were detected by Western Blot and protein interaction Was detected by immuno-precipitation.RESULTS:The research reports here for first time that β-arrestin 2 inhibits TNFα induced IKKα/β and its downstream signaling activation by interacting with RIP1 and inhibiting its polyubiquitination,promotes TAK1 and downstream signaling activation.Interfering the expression of β-arrestin 2 reverse above resuIts.CONCLUSION:β-arrestin 2 inhibits TNFαinduced IKKα/β activation and promotes TAK1 activation by interacting with RIP1 and inhibiting its polyubiquitination.
关键词
β-arrestin/2/肿瘤坏死因子/结肠癌/信号转导/泛素化Key words
β-arrestin 2/TNFα/colon cancer/signal transduction/ubiquitination引用本文复制引用
出版年
2009
NETL
NSTL
维普
万方数据