25 years of research put RIPK1 in the clinic

Lin Liu; Najoua Lalaoui

doi:10.1016/j.semcdb.2020.08.007

25 years of research put RIPK1 in the clinic

Semin Cell Dev Biol. 2021 Jan:109:86-95. doi: 10.1016/j.semcdb.2020.08.007. Epub 2020 Sep 13.

Authors

Lin Liu¹, Najoua Lalaoui²

Affiliations

¹ The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
² The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia. Electronic address: lalaoui@wehi.edu.au.

PMID: 32938551
DOI: 10.1016/j.semcdb.2020.08.007

Abstract

Receptor Interacting Protein Kinase 1 (RIPK1) is a key regulator of inflammation. To warrant cell survival and appropriate immune responses, RIPK1 is post-translationally regulated by ubiquitylations, phosphorylations and caspase-8-mediated cleavage. Dysregulations of these post-translational modifications switch on the pro-death function of RIPK1 and can cause inflammatory diseases in humans. Conversely, activation of RIPK1 cytotoxicity can be advantageous for cancer treatment. Small molecules targeting RIPK1 are under development for the treatment of cancer, inflammatory and neurogenerative disorders. We will discuss the molecular mechanisms controlling the functions of RIPK1, its pathologic role in humans and the therapeutic opportunities in targeting RIPK1, specifically in the context of inflammatory diseases and cancers.

Keywords: Apoptosis; Cancer; Inflammation; Necroptosis; PRR; RIPK1; TNF.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Humans
Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*
Time Factors

Substances

RIPK1 protein, human
Receptor-Interacting Protein Serine-Threonine Kinases