Phosphorylation of caspase-8 (Thr-263) by ribosomal S6 kinase 2 (RSK2) mediates caspase-8 ubiquitination and stability

J Biol Chem. 2011 Mar 4;286(9):6946-54. doi: 10.1074/jbc.M110.172338. Epub 2010 Dec 23.


The ribosomal S6 kinase 2 (RSK2) is a member of the p90 ribosomal S6 kinase (p90RSK) family of proteins and plays a critical role in proliferation, cell cycle, and cell transformation. Here, we report that RSK2 phosphorylates caspase-8, and Thr-263 was identified as a novel caspase-8 phosphorylation site. In addition, we showed that EGF induces caspase-8 ubiquitination and degradation through the proteasome pathway, and phosphorylation of Thr-263 is associated with caspase-8 stability. Finally, RSK2 blocks Fas-induced apoptosis through its phosphorylation of caspase-8. These data provide a direct link between RSK2 and caspase-8 and identify a novel molecular mechanism for caspase-8 modulation by RSK2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Caspase 8 / metabolism*
  • Cell Division / physiology
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Phosphorylation / physiology
  • Protein Stability
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism*
  • Signal Transduction / physiology*
  • Threonine / metabolism
  • Ubiquitination / physiology*


  • Threonine
  • Ribosomal Protein S6 Kinases, 90-kDa
  • ribosomal protein S6 kinase, 90kDa, polypeptide 3
  • CASP8 protein, human
  • Caspase 8