| Enzymatically active single chain caspase-8 maintains T-cell survival during clonal expansion. | |
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MedLine Citation:
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PMID: 20523353 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The extrinsic, or death receptor, pathway integrates apoptotic signals through the protease caspase-8 (casp8). Beyond cell death regulation, non-apoptotic functions of casp8 include its essential requirement for hematopoiesis and lymphocyte clonal expansion, and tempering of autophagy in T cells. However, the mechanistic basis for the control of these disparate cellular processes remains elusive. Here, we show that casp8-deficient T-cell survival was rescued by enzymatically active, but not inactive, casp8-expressing retroviruses. The casp8 catalytic induction in proliferating T cell occurred independent of extrinsic and intrinsic apoptotic-signaling cascades and did not induce casp8 proteolytic processing. Using a biotinylated probe selectively targeting enzymatically active caspases, catalytically active full-length casp8 was found in vivo in dividing T cells. A casp8 D387A processing mutant was able to rescue casp8-deficient T-cell proliferation, validating that casp8 self-processing is not required for its non-apoptotic function(s). Finally, casp8 activity was highest in CD8(+) T cells, the most rapidly proliferating subset. These results show that the catalytically competent form of casp8 is required for rapid T-cell proliferation in response to TCR ligation, but that processing of the caspase is only necessary to promote apoptosis. |
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Authors:
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S Leverrier; G S Salvesen; C M Walsh |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-06-04 |
Journal Detail:
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Title: Cell death and differentiation Volume: 18 ISSN: 1476-5403 ISO Abbreviation: Cell Death Differ. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-14 Completed Date: 2011-04-14 Revised Date: 2013-05-29 |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: England |
Other Details:
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Languages: eng Pagination: 90-8 Citation Subset: IM |
Affiliation:
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Department of Molecular Biology and Biochemistry, Institute for Immunology, University of California, Irvine, CA 92697-3900, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Substitution Animals Apoptosis CD8-Positive T-Lymphocytes / immunology, metabolism Caspase 8 / genetics, metabolism* Cell Proliferation Cell Survival Fas-Associated Death Domain Protein / metabolism Mice Mice, Transgenic Mutagenesis, Site-Directed Receptors, Antigen, T-Cell / metabolism T-Lymphocytes / cytology, enzymology*, immunology |
| Grant Support | |
ID/Acronym/Agency:
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AI50506/AI/NIAID NIH HHS; CA69381/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fadd protein, mouse; 0/Fas-Associated Death Domain Protein; 0/Receptors, Antigen, T-Cell; EC 3.4.22.-/Caspase 8 |
| Comments/Corrections | |
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