Necroptosis in development and diseases

Bing Shan, Heling Pan, Ayaz Najafov, Junying Yuan

Research output: Contribution to journalReview articlepeer-review

197 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)327-340
Number of pages14
JournalGenes and Development
Issue number5-6
StatePublished - Mar 1 2018
Externally publishedYes


  • Apoptosis
  • MLKL
  • Necroptosis
  • RIPK1
  • RIPK3

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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