Necroptosis Molecular Mechanisms: Recent Findings Regarding Novel Necroptosis Regulators

Overview

Journal Exp Mol Med

Specialties Biochemistry
Molecular Biology

Date 2021 Jun 2

PMID 34075202

Citations 91

Authors

Jinho Seo

Young Woo Nam

Seongmi Kim

Doo-Byoung Oh

Jaewhan Song

Affiliations

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Abstract

Necroptosis is a form of programmed necrosis that is mediated by various cytokines and pattern recognition receptors (PRRs). Cells dying by necroptosis show necrotic phenotypes, including swelling and membrane rupture, and release damage-associated molecular patterns (DAMPs), inflammatory cytokines, and chemokines, thereby mediating extreme inflammatory responses. Studies on gene knockout or necroptosis-specific inhibitor treatment in animal models have provided extensive evidence regarding the important roles of necroptosis in inflammatory diseases. The necroptosis signaling pathway is primarily modulated by activation of receptor-interacting protein kinase 3 (RIPK3), which phosphorylates mixed-lineage kinase domain-like protein (MLKL), mediating MLKL oligomerization. In the necroptosis process, these proteins are fine-tuned by posttranslational regulation via phosphorylation, ubiquitination, glycosylation, and protein-protein interactions. Herein, we review recent findings on the molecular regulatory mechanisms of necroptosis.

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