Cited by 784Cell death mechanisms and regulationT-cell and B-cell ImmunologyCancer-related Molecular Pathways

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

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Strasser, A., Harris, A. W., Huang, D. C., Krammer, P. H., Cory, S.·1995·The EMBO Journal

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.

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Crossref · 10.1002/j.1460-2075.1995.tb00304.x

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  • In type I cells (e.g., thymocytes and mature lymphocytes), CASP8-dependent proteolytic maturation of executioner CASP3 and CASP7 suffices to drive RCD, which cannot be inhibited by transgene-driven overexpression of anti-apoptotic BCL2 proteins, co-deletion of Bax and Bak1, or loss of BID.

    “In so-called “type I cells” (e.g., thymocytes and mature lymphocytes) the CASP8-dependent proteolytic maturation of executioner CASP3 and CASP7 suffices to drive RCD, which cannot be inhibited by the transgene-driven overexpression of anti-apoptotic BCL2 proteins, the co-deletion of Bax and Bak1, or the loss of BID [308, 309].”

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Research works printed but not linked: 3

  1. Jarvis,W.D., Kolesnick,R.N., Fornari,F.A., Traylor,R.S., Gewirtz,D.A. and Grant,S. (1994) Proc. Natl Acad. Sci. USA, 91, 73-77.
  2. Russell,J.H., Rush,B., Weaver,C. and Wang,R. (1993) Proc. Natl Acad. Sci. USA, 90, 4409-13.
  3. Strasser,A., Harris,A.W., Von Boehmer,H. and Cory,S. (1994) Proc. Natl Acad. Sci. USA, 91, 1376-1380.

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Authors
Strasser, A., Harris, A. W., Huang, D. C., Krammer, P. H., & Cory, S.
Affiliations
The Royal Melbourne Hospital (AU)
Venue
The EMBO Journal
Published
1995-12-01
Volume
14
Issue
24
Pages
6136-6147
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W1587890084
Cited by
784
References
83
Citations by year
2026: 7 · 2025: 6 · 2024: 4 · 2023: 9 · 2022: 13 · 2021: 10 · 2020: 12 · 2019: 6 · 2018: 11 · 2017: 11 · 2016: 10 · 2015: 4 · 2014: 10 · 2013: 15 · 2012: 79
FWCI
16.17
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation
  • Howard Hughes Medical Institute
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
  • Medical Research Council
  • National Health and Medical Research Council
  • National Cancer Institute (R01CA043540, CA 43540)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
Bcl-2, Fas/APO-1, lymphocyte apoptosis, CrmA, Bax, Bcl-x, lpr mice, T cell survival, thymocyte deletion, autoreactive T cells, immune regulation, radiation-induced cell death, serum deprivation
MeSH terms
Animals, Base Sequence, Cell Line, Humans, Lymphatic Diseases, Lymphocyte Activation, Lymphocytes, Mice, Transgenic, Molecular Sequence Data, Proto-Oncogene Proteins, Proto-Oncogenes, T-Lymphocytes, Viral Proteins, Signal Transduction, Autoimmunity, Serpins, Gene Expression, Apoptosis, DNA Primers, fas Receptor, Proto-Oncogene Proteins c-bcl-2, Mice

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