New role of E3 ubiquitin ligase in the regulation of necroptosis

Jinho Seo, Eun Woo Lee, Jaewhan Song

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8 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)247-248
Number of pages2
JournalBMB reports
Issue number5
Publication statusPublished - 2016 May 1

Bibliographical note

Funding Information:
This work was supported by a grant (NRF-2015R1A3A2066581 to J. Song) from the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning, Republic of Korea.

Publisher Copyright:
© 2016 by the The Korean Society for Biochemistry and Molecular Biology.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology


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