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Kinase-independent role of nuclear RIPK1 in regulating parthanatos through physical interaction with PARP1 upon oxidative stress.

Authors
  • Jang, Ki-Hong1
  • Jang, Taeik1
  • Son, Eunji1
  • Choi, Soonjin2
  • Kim, Eunhee3
  • 1 Department of Biological Sciences, Chungnam National University, Yuseong-gu, Daejeon 305-764, South Korea. , (North Korea)
  • 2 Graduate School of New Drug Discovery and Development, Chungnam National University, Yuseong-gu, Daejeon 305-764, South Korea. , (North Korea)
  • 3 Department of Biological Sciences, Chungnam National University, Yuseong-gu, Daejeon 305-764, South Korea. Electronic address: [email protected] , (North Korea)
Type
Published Article
Journal
Biochimica et Biophysica Acta
Publisher
Elsevier
Publication Date
Jan 01, 2018
Volume
1865
Issue
1
Pages
132–141
Identifiers
DOI: 10.1016/j.bbamcr.2017.10.004
PMID: 28993228
Source
Medline
Keywords
License
Unknown

Abstract

Regulated necrosis occurs in various pathophysiological conditions under oxidative stress. Here, we report that receptor-interacting protein kinase 1 (RIPK1), a key player in one type of regulated necrosis (necroptosis), also participates in another type of poly (ADP-ribose) polymerase 1 (PARP1)-dependent regulated necrosis (parthanatos). Various biological signatures of parthanatos were significantly attenuated in Ripk1-/- mouse embryonic fibroblasts, including PARylation, nuclear translocation of apoptosis-inducing factor, and PARP1-dependent cell death under H2O2 exposure. Hence, we investigated whether RIPK1 regulates the activity of PARP1. RIPK1 activated PARP1 via an interaction with the catalytic domain of PARP1 in the nucleus. Of note, both wild type and kinase-dead mutant RIPK1 induced PARP1 activation and led to PARP1-mediated cell death upon H2O2 insult, demonstrating the kinase-independent regulation of RIPK1 in PARP1 activation. Collectively, our results demonstrate the existence of a kinase-independent role of nuclear RIPK1 in the regulation of PARP1.

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