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Genes Dev. 2018 Mar 1;32(5-6):327-340. doi: 10.1101/gad.312561.118.

Necroptosis in development and diseases.

Author information

1
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, PuDong District, Shanghai 201203, China.
2
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
#
Contributed equally

Abstract

Necroptosis, a form of regulated necrotic cell death mediated by RIPK1 (receptor-interacting protein kinase 1) kinase activity, RIPK3, and MLKL (mixed-lineage kinase domain-like pseudokinase), can be activated under apoptosis-deficient conditions. Modulating the activation of RIPK1 by ubiquitination and phosphorylation is critical to control both necroptosis and apoptosis. Mutant mice with kinase-dead RIPK1 or RIPK3 and MLKL deficiency show no detrimental phenotype in regard to development and adult homeostasis. However, necroptosis and apoptosis can be activated in response to various mutations that result in the abortion of the defective embryos and human inflammatory and neurodegenerative pathologies. RIPK1 inhibition represents a key therapeutic strategy for treatment of diseases where blocking both necroptosis and apoptosis can be beneficial.

KEYWORDS:

MLKL; RIPK1; RIPK3; apoptosis; necroptosis

PMID:
29593066
PMCID:
PMC5900707
DOI:
10.1101/gad.312561.118
[Indexed for MEDLINE]
Free PMC Article

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