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

Biochim Biophys Acta Mol Cell Res

Department of Biological Sciences, Chungnam National University, Yuseong-gu, Daejeon 305-764, South Korea. Electronic address:

Published: January 2018

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 HO 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 HO 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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http://dx.doi.org/10.1016/j.bbamcr.2017.10.004DOI Listing

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