Format

Send to

Choose Destination
Mol Cell. 2005 Aug 5;19(3):321-32.

Phosphorylation of FADD at serine 194 by CKIalpha regulates its nonapoptotic activities.

Author information

1
The Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois 60637, USA.

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 Ialpha (CKIalpha) phosphorylates FADD at Ser194 both in vitro and in vivo. FADD-CKIalpha association regulates the subcellular localization of FADD, and phosphorylated FADD was found to colocalize with CKIalpha on the spindle poles in metaphase. Inhibition of CKIalpha 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.

PMID:
16061179
DOI:
10.1016/j.molcel.2005.06.024
[Indexed for MEDLINE]
Free full text

Publication types, MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center