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PMID: 9450996 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes.

The EMBO journal ·Vol. 17 ·No. 3 ·1998-02-02 ·Pages 706-18

Newton K, Harris AW, Bath ML, Smith KG, Strasser A

Abstract

Members of the tumour necrosis factor receptor family that contain a death domain have pleiotropic activities. They induce apoptosis via interaction with intracellular FADD/MORT1 and trigger cell growth or differentiation via TRADD and TRAF molecules. The impact of FADD/MORT1-transduced signals on T lymphocyte development was investigated in transgenic mice expressing a dominant negative mutant protein, FADD-DN. Unexpectedly, FADD-DN enhanced negative selection of self-reactive thymic lymphocytes and inhibited T cell activation by increasing apoptosis. Thus signalling through FADD/MORT1 does not lead exclusively to cell death, but under certain circumstances can promote cell survival and proliferation.

MeSH Terms
Adaptor Proteins, Signal Transducing Animals Apoptosis/drug effects,genetics,physiology Carrier Proteins/genetics,pharmacology,physiology Cell Division/drug effects,physiology Cells, Cultured Clone Cells/drug effects,physiology Fas-Associated Death Domain Protein Genes, Dominant/genetics,physiology Humans Lymphocyte Activation/drug effects Mice Mice, Inbred C57BL Mice, Inbred MRL lpr Mice, Transgenic Mitogens/pharmacology Mutation/genetics,physiology Serpins/genetics,physiology Superantigens/physiology T-Lymphocytes/drug effects,physiology Thymus Gland/cytology,drug effects,immunology Transduction, Genetic fas Receptor/genetics,pharmacology
Chemicals
Adaptor Proteins, Signal Transducing Carrier Proteins FADD protein, human Fadd protein, mouse Fas-Associated Death Domain Protein Mitogens Serpins Superantigens fas Receptor
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Newton K
The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia.
Harris A W
Bath M L
Smith K G
Strasser A
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/17.3.706
Published
1998-02-02
Pages
706-18
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170420
Subset
IM
Grants
NCI NIH HHS · CA43540 · United States
External Links
PubMed source DOI: 10.1093/emboj/17.3.706 PMC Full Text View journal details
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