title: Complex Pathologic Roles of RIPK1 and RIPK3: Moving Beyond Necroptosis.
abstract: A process of regulated necrosis, termed necroptosis, has been recognized as a major contributor to cell death and inflammation occurring under a wide range of pathologic settings. The core event in necroptosis is the formation of the detergent-insoluble 'necrosome' complex of homologous Ser/Thr kinases, receptor protein interacting kinase 1 (RIPK1) and receptor interacting protein kinase 3 (RIPK3), which promotes phosphorylation of a key prodeath effector, mixed lineage kinase domain-like (MLKL), by RIPK3. Core necroptosis mediators are under multiple controls, which have been a subject of intense investigation. Additional, non-necroptotic functions of these factors, primarily in controlling apoptosis and inflammatory responses, have also begun to emerge. This review will provide an overview of the current understanding of the human disease relevance of this pathway, and potential therapeutic strategies, targeting necroptosis mediators in various pathologies.
authors.affiliation: Master of Science in Biomedical Sciences Program, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Kelby W
authors.initials: KW
authors.lastname: Wegner
authors.affiliation: Medical Scientist Training Program and Program in Neuroscience, Sackler Graduate School, Tufts University, Boston, MA 02111, USA.
authors.forename: Danish
authors.initials: D
authors.lastname: Saleh
authors.affiliation: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA. Electronic address: alexei.degterev@tufts.edu.
authors.forename: Alexei
authors.initials: A
authors.lastname: Degterev
mesh_terms: D000818:Animals; D006801:Humans; D009336:Necrosis / Q000201:enzymology*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C506249:RIPK1 protein, human; C119705:RIPK3 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506251:Ripk1 protein, mouse; C485615:Ripk3 protein, mouse