New role of E3 ubiquitin ligase in the regulation of necroptosis

BMB Reports

Jinho Seo^1¹ 

[1] Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea^1

关键词: CHIP;   

DOI  :  

学科分类：生物化学/生物物理

来源: Korean Society for Biochemistry and Molecular Biology

【 摘 要 】

Necroptosis is a well-known form of caspase-independent cell death. Necroptosis can be triggered by various extrinsic stimuli, including death ligands in the presence of receptorinteracting protein kinase 3 (RIPK3), a key mediator of necroptosis induction. Our recent studies have revealed that C-terminus HSC-70 interacting protein (CHIP), an E3 ligase, can function as an inhibitor of necroptosis. CHIP?/? mouse embryonic fibroblast showed higher sensitivity to necrotic stimuli than wild-type mouse embryonic fibroblast cells. Deleterious effects of CHIP knockout MEFs were retrieved by RIPK3 depletion. We found that CHIP negatively regulated RIPK3 and RIPK1 by ubiquitylation- and lysosome- dependent degradation. In addition, CHIP?/? mice showed postnatal lethality with intestinal defects that could be rescued by crossing with RIPK3?/? mice. These results suggest that CHIP is a negative regulator of RIPK1 and RIPK3, thus inhibiting necroptosis.

【 授权许可】

Unknown