A function of Fas-associated death domain protein in cell cycle progression localized to a single amino acid at its C-terminal region.
FADD is an adaptor known to transmit apoptotic signals from members of the tumor necrosis factor receptor family. We show here that FADD has a domain implicated in cell proliferation. Mice bearing the Asp mutation in the serine 191 phosphorylation site are runted and anemic and display splenomegaly. Apoptosis is unimpaired in these mice, but they exhibit many immune developmental problems indicative of proliferative defects. Mutant FADD T cells are defective in cell cycle progression, suggesting that regulation of phosphorylation at serine 191 is essential for growth/proliferation. Remarkably, serine 191 is conserved among mammalian FADD proteins, but this C-terminal region is absent in lower organisms, suggesting that FADD acquired a domain during evolution, rendering it a "proliferation-apoptosis coupler" that balances cell proliferation and apoptosis.
Hua
Zi Chun
ZC
Department of Molecular and Cell Biology, Division of Immunology and Cancer Research Laboratory, 469 LSA, University of California, Berkeley 94720, USA.
Sohn
Sue J
SJ
Kang
Chulho
C
Cado
Dragana
D
Winoto
Astar
A
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000740:Anemia / Q000209:etiology; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002453:Cell Cycle; D002455:Cell Division; D053200:Fas-Associated Death Domain Protein; D051379:Mice; D008969:Molecular Sequence Data; D013163:Splenomegaly / Q000209:etiology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein