Activity of Protein Kinase RIPK3 Determines Whether Cells Die by Necroptosis or Apoptosis

TLDR

RIPK1 and RIPK3 are kinases that drive necroptotic cell death, and blocking one form of death can trigger another. Inhibition of RIPK3 can paradoxically increase apoptosis; mice with kinase‑dead RIPK3 die from apoptosis, whereas RIPK3‑null mice survive, indicating RIPK3 also restrains caspase‑8–mediated apoptosis. The study is cited in a Perspective by Zhang and Chan (p.

Abstract

Life and Cell Death Trying to protect animals from one form of cell death may lead to death by another. Two protein kinases, known as RIPK1 and RIPK3 promote signaling that leads to cell death by necroptosis. However, Newton et al. (p. 1357 , published online 20 February; see the Perspective by Zhang and Chan ) found that inhibition of RIPK3 was not always beneficial. Instead, mice expressing a form of RIPK3 with no catalytic activity died from increased apoptotic cell death, but animals lacking the RIPK3 protein entirely, did not die perhaps because RIPK3 restrains apoptosis mediated by caspase-8 by an independent mechanism.