title: Necroptosis: Pathway diversity and characteristics.
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.
authors: Early Discovery Biochemistry, Genentech, South San Francisco, CA 94080, USA.
authors: M Cristina
authors: MC
authors: de Almagro
authors: Early Discovery Biochemistry, Genentech, South San Francisco, CA 94080, USA. Electronic address: domagoj@gene.com.
authors: Domagoj
authors: D
authors: Vucic
mesh_terms: D000818:Animals; D016923:Cell Death; D006801:Humans; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D053422:Receptor-Interacting Protein Serine-Threonine Kinases
keywords: MLKL; Necroptosis; RIP1; RIP3; TNF