Document Detail

A Fas-associated death domain protein/caspase-8-signaling axis promotes S-phase entry and maintains S6 kinase activity in T cells responding to IL-2.
MedLine Citation:
PMID:  17911615     Owner:  NLM     Status:  MEDLINE    
Fas-associated death domain protein (FADD) constitutes an essential component of TNFR-induced apoptotic signaling. Paradoxically, FADD has also been shown to be crucial for lymphocyte development and activation. In this study, we report that FADD is necessary for long-term maintenance of S6 kinase (S6K) activity. S6 phosphorylation at serines 240 and 244 was only observed after long-term stimulation of wild-type cells, roughly corresponding to the time before S-phase entry, and was poorly induced in T cells expressing a dominantly interfering form of FADD (FADDdd), viral FLIP, or possessing a deficiency in caspase-8. Defects in S6K1 phosphorylation were also observed. However, defective S6K1 phosphorylation was not a consequence of a wholesale defect in mammalian target of rapamycin function, because 4E-BP1 phosphorylation following T cell activation was unaffected by FADDdd expression. Although cyclin D3 up-regulation and retinoblastoma hypophosphorylation occurred normally in FADDdd T cells, cyclin E expression and cyclin-dependent kinase 2 activation were markedly impaired in FADDdd T cells. These results demonstrate that a FADD/caspase-8-signaling axis promotes T cell cycle progression and sustained S6K activity.
Adrian F Arechiga; Bryan D Bell; Sabrina Leverrier; Brian M Weist; Melissa Porter; Zhengqi Wu; Yuka Kanno; Stephanie J Ramos; S Tiong Ong; Richard Siegel; Craig M Walsh
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  179     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-03     Completed Date:  2007-11-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5291-300     Citation Subset:  AIM; IM    
Department of Molecular Biology and Biochemistry, Center for Immunology, University of California, Irvine, CA 92697, USA.
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MeSH Terms
Alstrom Syndrome
Caspase 8 / genetics,  physiology*
Cells, Cultured
Cyclin-Dependent Kinase 2 / deficiency,  metabolism,  physiology
Enzyme Activation / genetics,  immunology
Fas-Associated Death Domain Protein / physiology*
Interleukin-2 / physiology*
Mice, Inbred C57BL
Mice, Transgenic
Ribosomal Protein S6 Kinases / deficiency,  metabolism*
S Phase / genetics,  immunology*
Signal Transduction / genetics,  immunology*
T-Lymphocyte Subsets / cytology*,  enzymology*,  immunology
Grant Support
Reg. No./Substance:
0/Fadd protein, mouse; 0/Fas-Associated Death Domain Protein; 0/Interleukin-2; EC Protein S6 Kinases; EC Kinase 2; EC 3.4.22.-/Casp8 protein, mouse; EC 3.4.22.-/Caspase 8

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