Cell cycle effects by C-FADD depend on its C-terminal phosphorylation site.
Expression of a truncated form of the death receptor adaptor FADD (C-FADD) as a transgene in mice blocks T cell proliferation. Here we provide evidence that the C-terminal phosphorylation site Ser194 in C-FADD affects the cell cycle in nonlymphoid cells as well. High expression of wild type C-FADD but not C-FADD with a S194A point mutation arrested the nontumor cell line MCF10A in G2/M but not the tumor cell line MCF7. BJAB as well as MCF10A cells expressing moderate levels of C-FADD with a S194E mutation mimicking phosphorylated C-FADD were more susceptible to a Taxol-induced G2/M arrest than cells expressing C-FADD S194A suggesting that C-FADD S194E lowers the threshold for G2/M arrest. Our data suggest that C-FADD may affect apoptosis sensitivity of cells by interfering with cell cycle progression and not only by binding to death receptors.
Alappat
Elizabeth C
EC
The Ben May Institute for Cancer Research, University of Chicago, 924 E. 57th Street, Chicago, IL 60637, USA.
Volkland
Jörg
J
Peter
Marcus E
ME
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D017209:Apoptosis; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D053200:Fas-Associated Death Domain Protein; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D007399:Interphase; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D014161:Transduction, Genetic
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D017239:Paclitaxel