New role of E3 ubiquitin ligase in the regulation of necroptosis.
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. [BMB Reports 2016; 49(5): 247-248].
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Jinho
J
Seo
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Eun-Woo
EW
Lee
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Jaewhan
J
Song
D000818:Animals; D017209:Apoptosis; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009336:Necrosis; D059748:Proteolysis; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
C492951:Stub1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D053422:Receptor-Interacting Protein Serine-Threonine Kinases