| Cytokine suppression of protease activation in wild-type p53-dependent and p53-independent apoptosis. | |
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MedLine Citation:
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PMID: 9256485 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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M1 myeloid leukemic cells overexpressing wild-type p53 undergo apoptosis. This apoptosis can be suppressed by some cytokines, protease inhibitors, and antioxidants. We now show that induction of apoptosis by overexpressing wild-type p53 is associated with activation of interleukin-1beta-converting enzyme (ICE)-like proteases, resulting in cleavage of poly(ADP- ribose) polymerase and the proenzyme of the ICE-like protease Nedd-2. Activation of these proteases and apoptosis were suppressed by the cytokine interleukin 6 or by a combination of the cytokine interferon gamma and the antioxidant butylated hydroxyanisole, and activation of poly(ADP-ribose) polymerase and apoptosis were suppressed by some protease inhibitors. In a clone of M1 cells that did not express p53, vincristine or doxorubicin induced protease activation and apoptosis that were not suppressed by protease inhibitors, but were suppressed by interleukin 6. In another myeloid leukemia (7-M12) doxorubicin also induced protease activation and apoptosis that were not suppressed by protease inhibitors, but were suppressed by granulocyte-macrophage colony-stimulating factor. The results indicate that (i) overexpression of wild-type p53 by itself or treatment with cytotoxic compounds in wild-type p53-expressing or p53-nonexpressing myeloid leukemic cells is associated with activation of ICE-like proteases; (ii) cytokines exert apoptosis-suppressing functions upstream of protease activation; (iii) the cytotoxic compounds induce additional pathways in apoptosis; and (iv) cytokines can also suppress these other components of the apoptotic machinery. |
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Authors:
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J Lotem; L Sachs |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 94 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 1997 Aug |
Date Detail:
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Created Date: 1997-09-17 Completed Date: 1997-09-17 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 9349-53 Citation Subset: IM |
Affiliation:
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Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis* / drug effects Caspase 2 Caspases* Cysteine Endopeptidases / physiology Cytokines / pharmacology*, physiology Enzyme Activation Mice Proteins / physiology* Tumor Cells, Cultured Tumor Suppressor Protein p53 / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Proteins; 0/Tumor Suppressor Protein p53; EC 3.4.22.-/Caspase 2; EC 3.4.22.-/Caspases; EC 3.4.22.-/Cysteine Endopeptidases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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