期刊
CELL RESEARCH
卷 20, 期 4, 页码 421-433出版社
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2010.18
关键词
HtrA2/Omi; RIP1; Ba/F3; IL-3; apoptosis
类别
资金
- Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT)
- Stichting Emmanuel van der Schueren
- Flanders Institute for Biotechnology (VIB)
- European Union [MRTN-CT-035624]
- EC [LSHB-CT-2005-019067]
- APO-SYS [HEALTH-F4-2007-200767]
- Interuniversity Poles of Attraction-Belgian Science Policy [IAP6/18]
- FWO [3G.0218.06]
- Ghent University [12.0505.02]
Interleukin-3 (IL-3) deprivation of the mouse pro-B cell line Ba/F3 induces cell death that is abrogated by B-cell lymphoma 2 (Bcl-2) overexpression, but remains unaffected by the pan-caspase inhibitor carbobenzoxy-valyl-analylaspartyl-[O-methyl]-fluoromethylketone (zVAD-fmk). IL-3 withdrawal causes receptor-interacting protein (RIP) 1 cleavage into C-terminal fragments of 30 and 25 kDa, and only cleavage leading to the former was prevented by zVAD-fmk. siRNA experiments demonstrated that generation of the 25-kDa fragment was due to a Bcl-2-modulated release of the mitochondrial serine protease high temperature requirement protein A2 (HtrA2)/Omi. Accordingly, recombinant HtrA2/Omi efficiently cleaved mouse RIP1 in vitro, generating fragments matching those observed in IL-3-deprived Ba/F3 cells. The HtrA2/Omi cleavage site in mouse RIP1 was mapped to the intermediate domain and the corresponding N- and C-terminal fragments were impaired in their ability to activate nuclear factor-kappa B, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. Interestingly, knockdown of HtrA2/Omi afforded protection against IL-3 withdrawal-induced death in the presence of zVAD-fmk, demonstrating a role for HtrA2/Omi in caspase-independent cell death during growth factor withdrawal by cleaving RIP1.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据