Necroptosis molecular mechanisms: Recent findings regarding novel necroptosis regulators.

Jinho Seo, Young Woo Nam, Seongmi Kim, Doo-Byoung Oh, Jaewhan Song

Experimental & molecular medicine 2021 Jun

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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.

Citation

Jinho Seo, Young Woo Nam, Seongmi Kim, Doo-Byoung Oh, Jaewhan Song. Necroptosis molecular mechanisms: Recent findings regarding novel necroptosis regulators. Experimental & molecular medicine. 2021 Jun;53(6):1007-1017