Phosphorylation of FADD at serine 194 by CKIα regulates its nonapoptotic activities

Elizabeth C. Alappat, Christine Feig, Benjamin Boyerinas, Jörg Volkland, Martin Samuels, Andrea E. Murmann, Andrew Thorburn, Vincent J. Kidd, Clive A. Slaughter, Stephanie L. Osborn, Astar Winoto, Wei Jen Tang, Marcus E. Peter

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113 Scopus citations

Abstract

FADD is essential for death receptor (DR)-induced apoptosis. However, it is also critical for cell cycle progression and proliferation, activities that are regulated by phosphorylation of its C-terminal Ser194, which has also been implicated in sensitizing cancer cells to chemotherapeutic drugs and in regulating FADD's intracellular localization. We now demonstrate that casein kinase Iα (CKIα) phosphorylates FADD at Ser194 both in vitro and in vivo. FADD-CKIα association regulates the subcellular localization of FADD, and phosphorylated FADD was found to colocalize with CKIα on the spindle poles in metaphase. Inhibition of CKIα diminished FADD phosphorylation, prevented the ability of Taxol to arrest cells in mitosis, and blocked mitogen-induced proliferation of mouse splenocytes. In contrast, a low level of cycling splenocytes from mice expressing FADD with a mutated phosphorylation site was insensitive to CKI inhibition. These data suggest that phosphorylation of FADD by CKI is a crucial event during mitosis.

Original languageEnglish (US)
Pages (from-to)321-332
Number of pages12
JournalMolecular Cell
Volume19
Issue number3
DOIs
Publication statusPublished - Aug 5 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Alappat, E. C., Feig, C., Boyerinas, B., Volkland, J., Samuels, M., Murmann, A. E., ... Peter, M. E. (2005). Phosphorylation of FADD at serine 194 by CKIα regulates its nonapoptotic activities. Molecular Cell, 19(3), 321-332. https://doi.org/10.1016/j.molcel.2005.06.024