RIP3, a novel apoptosis-inducing kinase

J Biol Chem. 1999 Jun 11;274(24):16871-5. doi: 10.1074/jbc.274.24.16871.

Abstract

RIP3 is a novel gene product containing a N-terminal kinase domain that shares extensive homology with the corresponding domain in RIP (receptor-interacting protein) and RIP2. Unlike RIP, which has a C-terminal death domain, and RIP2, which has a C-terminal caspase activation and recruitment domain, RIP3 has a unique C terminus. RIP3 binds RIP through its unique C-terminal segment and by virtue of this interaction is recruited to the tumor necrosis factor (TNF) receptor-1 signaling complex. Previous studies have shown that RIP mediates TNF-induced activation of the anti-apoptotic NF-kappaB pathway. RIP3, however, attenuates both RIP and TNF receptor-1-induced NF-kappaB activation. Overexpression studies revealed RIP3 to be a potent inducer of apoptosis, capable of selectively binding to large prodomain initiator caspases.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / metabolism
  • Apoptosis*
  • Caspases / metabolism
  • Cloning, Molecular
  • Humans
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Protein Binding
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein Serine-Threonine Kinases
  • Proteins / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Proteins / metabolism
  • Sequence Analysis
  • Sequence Homology, Amino Acid
  • Signal Transduction

Substances

  • Antigens, CD
  • NF-kappa B
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Proteins
  • Protein Kinases
  • Protein Serine-Threonine Kinases
  • RIPK1 protein, human
  • RIPK2 protein, human
  • RIPK3 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Caspases

Associated data

  • GENBANK/AA227673
  • GENBANK/AI082587
  • GENBANK/AI394293