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PMID: 8557033 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis.

The EMBO journal ·Vol. 14 ·No. 24 ·1995-12-15 ·Pages 6136-47

Strasser A, Harris AW, Huang DC, Krammer PH, Cory S

Abstract

Activation of the cell surface receptor Fas/APO-1 (CD95) induces apoptosis in lymphocytes and regulates immune responses. The cytoplasmic membrane protein Bcl-2 inhibits lymphocyte killing by diverse cytotoxic agents, but we found it provided little protection against Fas/APO-1-transduced apoptosis in B lymphoid cell lines, thymocytes and activated T cells. In contrast, the cowpox virus protease inhibitor CrmA blocked Fas/APO-1-transduced apoptosis, but did not affect cell death induced by gamma-radiation or serum deprivation. Signalling through Fas/APO-1 did not down-regulate Bcl-2 or induce its antagonists Bax and Bcl-xS. In Fas/APO-1-deficient lpr mice, Bcl-2 transgenes markedly augmented the survival of antigen-activated T cells and the abnormal accumulation of lymphocytes (although they did not interfere with deletion of auto-reactive cells in the thymus). These data raise the possibility that Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis.

MeSH Terms
Animals Apoptosis/genetics,immunology,physiology Autoimmunity Base Sequence Cell Line DNA Primers/genetics Gene Expression Humans Lymphatic Diseases/etiology Lymphocyte Activation Lymphocytes/cytology,immunology,physiology Mice Mice, Transgenic Molecular Sequence Data Proto-Oncogene Proteins/genetics,physiology Proto-Oncogene Proteins c-bcl-2 Proto-Oncogenes Serpins/physiology Signal Transduction/physiology T-Lymphocytes/immunology Viral Proteins fas Receptor/genetics,physiology
Chemicals
DNA Primers Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Serpins Viral Proteins fas Receptor interleukin-1beta-converting enzyme inhibitor
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Strasser A
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Harris A W
Huang D C
Krammer P H
Cory S
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1995-12-15
Pages
6136-47
Language
English
Region
England
NLM ID
8208664
PMCID
PMC394738
Subset
IM
Grants
NCI NIH HHS · CA43540 · United States
External Links
PubMed source PMC Full Text View journal details
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