| Baculovirus P35 inhibits the glucocorticoid-mediated pathway of cell death. | |
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MedLine Citation:
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PMID: 8988038 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recent evidence suggests that members of the interleukin-1-beta-converting enzyme (ICE)/Ced-3 family are key mediators of mammalian apoptosis. The known members of the ICE/Ced-3 cysteine protease family are synthesized as proenzymes and require proteolytic processing to produce active, heterodimeric enzymes. The baculovirus protein P35 has recently been shown to inhibit several members of the ICE/Ced-3 cysteine protease family. The importance of ICE/Ced-3 cysteine proteases in programmed cell death prompted us to investigate the role of the apoptotic mediator, CPP32, in the glucocorticoid-mediated cell death pathway. Glucocorticoids induce growth inhibition and apoptosis in sensitive leukemic cell lines, immature thymocytes, and eosinophils. In this report, we demonstrate the enzymatic cleavage of proCPP32 to its active subunits in cells undergoing glucocorticoid-induced apoptotic cell death. Concurrently, in apoptotic cells, PARP, a 116-kilodalton (kDa) human poly(ADP-ribose) polymerase, is proteolytically cleaved to its signature 85-kDa fragment. The proteolytic processing of PARP (the nuclear DNA repair enzyme known to be cleaved in association with apoptosis) is catalyzed by members of the ICE/Ced-3 family. Importantly, stable transfection of the antiapoptotic baculovirus P35 inhibits glucocorticoid-induced apoptotic cell death, proteolytic processing of proCPP32, and cleavage of the 116kDa PARP. We conclude that activation of CPP32 is a critical event in glucocorticoid-induced apoptosis and that this pathway is inhibited at or upstream of CPP32 by baculovirus P35. These data demonstrate that PARP cleavage occurs during glucocorticoid-induced apoptotic cell death and show that this proteolytic process is blocked by the expression of baculovirus P35, supporting a role for activation of the ICE/Ced-3-like cysteine protease during glucocorticoid-induced apoptosis. |
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Authors:
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N M Robertson; J Zangrilli; T Fernandes-Alnemri; P D Friesen; G Litwack; E S Alnemri |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cancer research Volume: 57 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1997 Jan |
Date Detail:
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Created Date: 1997-01-28 Completed Date: 1997-01-28 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 43-7 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Pharmacology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects,
physiology* Caenorhabditis elegans Proteins Caspase 3 Caspases* Cell Division Cysteine Endopeptidases / metabolism*, physiology* Cysteine Proteinase Inhibitors / physiology DNA Fragmentation Enzyme Activation Glucocorticoids / pharmacology Helminth Proteins / antagonists & inhibitors, physiology* Humans Inhibitor of Apoptosis Proteins Poly(ADP-ribose) Polymerases / metabolism Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics, pathology Tumor Cells, Cultured Viral Proteins / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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AI35035-03/AI/NIAID NIH HHS; DK44441-03/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Caenorhabditis elegans Proteins; 0/Cysteine Proteinase Inhibitors; 0/Glucocorticoids; 0/Helminth Proteins; 0/Inhibitor of Apoptosis Proteins; 0/Viral Proteins; 0/inhibitor of apoptosis, Nucleopolyhedrovirus; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.22.-/ced-3 protein, C elegans |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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