Cellular FLIP long form augments caspase activity and death of T cells through heterodimerization with and activation of caspase-8
Détails
ID Serval
serval:BIB_1EA8FD743E60
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Cellular FLIP long form augments caspase activity and death of T cells through heterodimerization with and activation of caspase-8
Périodique
Journal of Immunology
ISSN
0022-1767 (Print)
Statut éditorial
Publié
Date de publication
07/2005
Volume
175
Numéro
1
Pages
311-8
Notes
In Vitro
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jul 1
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jul 1
Résumé
Caspase activity is required not only for the death of T cells, but also for their activation. A delicate balance of caspase activity is thus required during T cell activation at a level that will not drive cell death. How caspase activity is initiated and regulated during T cell activation is not known. One logical candidate for this process is cellular FLIP long form (c-FLIP(L)), because it can block caspase-8 recruitment after Fas (CD95) ligation as well as directly heterodimerize with and activate caspase-8. The current findings demonstrate that after T cell activation, caspase-8 and c-FLIP(L) associate in a complex enriched for active caspases. This occurs coincidently with the cleavage of two known caspase-8 substrates, c-FLIP(L) and receptor interacting protein 1. Caspase activity is higher in wild-type CD8(+) than CD4(+) effector T cells. Increased expression of c-FLIP(L) results in augmented caspase activity in resting and effector T cells to levels that provoke cell death, especially of the CD8 subset. c-FLIP(L) is thus not only an inhibitor of cell death by Fas, it can also act as a principal activator of caspases independently of Fas.
Mots-clé
Animals
Antigens, CD95/metabolism
Base Sequence
CASP8 and FADD-Like Apoptosis Regulating Protein
CD4-Positive T-Lymphocytes/cytology/immunology/metabolism
CD8-Positive T-Lymphocytes/cytology/immunology/metabolism
Caspase 8
Caspases/*chemistry/*metabolism
Cell Death
Cell Proliferation
DNA, Complementary/genetics
Dimerization
Enzyme Activation
Intracellular Signaling Peptides and Proteins/*chemistry/*metabolism
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Transgenic
T-Lymphocytes/*cytology/immunology/*metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 16:19
Dernière modification de la notice
20/08/2019 13:54