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KMID : 0624620160490050247
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BMB Reports
2016 Volume.49 No. 5 p.247 ~ p.248
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New role of E3 ubiquitin ligase in the regulation of necroptosis
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Seo Jin-Ho
Lee Eun-Woo
Song Jae-Whan
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Abstract
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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.
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KEYWORD
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CHIP, Lysosome, Necroptosis, RIPK3, Ubiquitylation
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