DOI QR코드

DOI QR Code

New role of E3 ubiquitin ligase in the regulation of necroptosis

  • Seo, Jinho (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Lee, Eun-Woo (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Song, Jaewhan (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University)
  • 투고 : 2016.04.14
  • 발행 : 2016.05.31

초록

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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피인용 문헌

  1. Negative regulators of cell death pathways in cancer: perspective on biomarkers and targeted therapies vol.23, pp.2, 2018, https://doi.org/10.1007/s10495-018-1440-4
  2. Anisomycin prevents OGD-induced necroptosis by regulating the E3 ligase CHIP vol.8, pp.1, 2018, https://doi.org/10.1038/s41598-018-24414-y