Necroptosis: Pathway diversity and characteristics

M Cristina de Almagro; Domagoj Vucic

doi:10.1016/j.semcdb.2015.02.002

Necroptosis: Pathway diversity and characteristics

Semin Cell Dev Biol. 2015 Mar:39:56-62. doi: 10.1016/j.semcdb.2015.02.002. Epub 2015 Feb 13.

Authors

M Cristina de Almagro¹, Domagoj Vucic²

Affiliations

¹ Early Discovery Biochemistry, Genentech, South San Francisco, CA 94080, USA.
² Early Discovery Biochemistry, Genentech, South San Francisco, CA 94080, USA. Electronic address: domagoj@gene.com.

PMID: 25683283
DOI: 10.1016/j.semcdb.2015.02.002

Abstract

Regulated cell death is a physiological process that controls organismal homeostasis. Deregulation of cell death can lead to the development of a number of human diseases and tissue damage. Apoptosis is a best-known model of caspase-dependent regulated cell death, but recently necroptosis has garnered a lot of attention as a form of regulated cell death not mediated by caspases. Different stimuli can trigger necroptosis, and all of them converge at the activation of the protein kinase RIP3 (receptor-interacting protein 3) and the pseudokinase MLKL (mixed lineage kinase domain-like). Necroptosis activation relies on the unique protein-interaction motif RHIM (RIP homology interaction motif). Different RHIM-containing proteins (RIP1, DAI and TRIF) transduce necroptotic signals from the cell death trigger to the cell death mediators RIP3-MLKL. RIP1 has a particularly important and complex role in necroptotic cell death regulation ranging from cell death activation to inhibition, often in a cell type and context dependent fashion.

Keywords: MLKL; Necroptosis; RIP1; RIP3; TNF.

Publication types

Review

MeSH terms

Animals
Cell Death*
Humans
Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
Signal Transduction

Substances

Receptor-Interacting Protein Serine-Threonine Kinases