RIPK1

A gene on chromosome 6p25.2 that encodes a serine/threonine/tyrosine kinase which transduces inflammatory and cell-death signals (necroptosis), triggered in response to the binding of ligands to death receptors, activation of pathogen recognition receptors (PRRs) and DNA damage. Activation of TNFR1 by TNF-alpha family cytokines recruits TRADD and TRAF2 to the receptor; ubiquitination by TRAF2 enhances communication with downstream signal transducers in the mitogen-activated protein kinase (MAPK) and NF-kappaB pathways, activating genes that encode inflammatory molecules. Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory subunit of the IKK complex, a critical event for NF-kappaB activation. Interaction with other cellular RHIM-containing adapters initiates gene activation and cell death. RIPK1 and RIPK3 form a necroptosis-inducing complex.

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References in periodicals archive

A recent study has shown that acidosis-induced necroptosis in neurons is dependent on acid-sensing ion channel 1a- (ASIC1a-) mediated RIPK1 phosphorylation [69].

Werner et al., "RIPK1 both positively and negatively regulates RIPK3 oligomerization and necroptosis," Cell Death and Differentiation, vol.

Caption: Figure 4: RIPK1 cleavage at pH 7.4 and 6.7.

Intracellular pH Regulates TRAIL-Induced Apoptosis and Necroptosis in Endothelial Cells

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