BMB Rep. 2016; 49(5): 247-248  
New role of E3 ubiquitin ligase in the regulation of necroptosis
Jinho Seo, Eun-Woo Lee & Jaewhan Song*
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea
Correspondence to: E-mail: jso678@yonsei.ac.kr
Received: April 14, 2016; Published online: May 31, 2016.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

Abstract
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.
Keywords: CHIP, Lysosome, Necroptosis, RIPK3, Ubiquitylation


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