The Regulation of Necroptosis by Post-Translational Modifications of RIPK3

GAO Xuming¹, SHEN Binhua², HU Jinfeng¹*, HU Xiangming¹*

(¹ Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China; ² Department of Rheumatology and Immunology, Jiangxi Provincial People’s Hospital, the First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, China)

Abstract:

Necroptosis is a caspase-independent programmed cell death which has been widely implicated in many pathologies, such as viral or pathogen infection, atherosclerosis, cardiac ischemia-reperfusion and cancer. RIPK3 (receptor-interacting protein kinase 3) has emerged as a critical regulator of necroptosis, which can interact with RIPK1 (receptor-interacting protein kinase 1) to form a protein complex called necrosome and then active MLKL (mixed lineage kinase domain-like pseudokinase) to cause plasma membrane rupture and cell death. In recent years, increasing studies have found that the activity of RIPK3 is regulated by multiple post-translational modifications, including phosphorylation, ubiquitylation, GlcNAcylation and proteolytic cleavage. This article reviews the role of post-translational modifications of RIPK3 in necroptosis, which may provide theoretical basis for drug design targeting RIPK3 and treatment of necroptosis-related diseases.

CSTR: 32200.14.cjcb.2023.01.0013