Inhibition of death receptor signals by cellular FLIP.

Details

Ressource 1Download: BIB_B780D8F4383C.P001.pdf (679.98 [Ko])
State: Public
Version: author
Serval ID
serval:BIB_B780D8F4383C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Inhibition of death receptor signals by cellular FLIP.
Journal
Nature
Author(s)
Irmler M., Thome M., Hahne M., Schneider P., Hofmann K., Steiner V., Bodmer J.L., Schröter M., Burns K., Mattmann C., Rimoldi D., French L.E., Tschopp J.
ISSN
0028-0836 (Print)
ISSN-L
0028-0836
Publication state
Published
Issued date
1997
Volume
388
Number
6638
Pages
190-195
Language
english
Abstract
The widely expressed protein Fas is a member of the tumour necrosis factor receptor family which can trigger apoptosis. However, Fas surface expression does not necessarily render cells susceptible to Fas ligand-induced death signals, indicating that inhibitors of the apoptosis-signalling pathway must exist. Here we report the characterization of an inhibitor of apoptosis, designated FLIP (for FLICE-inhibitory protein), which is predominantly expressed in muscle and lymphoid tissues. The short form, FLIPs, contains two death effector domains and is structurally related to the viral FLIP inhibitors of apoptosis, whereas the long form, FLIP(L), contains in addition a caspase-like domain in which the active-centre cysteine residue is substituted by a tyrosine residue. FLIPs and FLIP(L) interact with the adaptor protein FADD and the protease FLICE, and potently inhibit apoptosis induced by all known human death receptors. FLIP(L) is expressed during the early stage of T-cell activation, but disappears when T cells become susceptible to Fas ligand-mediated apoptosis. High levels of FLIP(L) protein are also detectable in melanoma cell lines and malignant melanoma tumours. Thus FLIP may be implicated in tissue homeostasis as an important regulator of apoptosis.
Keywords
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Antigens, CD95/metabolism, Apoptosis, CASP8 and FADD-Like Apoptosis Regulating Protein, Carrier Proteins/genetics, Carrier Proteins/metabolism, Caspase 8, Caspase 9, Caspases, Cells, Cultured, Chromosomes, Human, Pair 2, Cloning, Molecular, Cysteine Endopeptidases/metabolism, Fas-Associated Death Domain Protein, Humans, Intracellular Signaling Peptides and Proteins, Lymphocyte Activation, Melanoma/metabolism, Molecular Sequence Data, Sequence Homology, Amino Acid, T-Lymphocytes/cytology, T-Lymphocytes/immunology, Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:18
Last modification date
20/08/2019 15:25
Usage data