| DNA-dependent protein kinase is one of a subset of autoantigens specifically cleaved early during apoptosis. | |
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MedLine Citation:
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PMID: 7500007 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Proteolytic cleavage of key substrates appears to be an important biochemical mechanism underlying the apoptotic process, and the centrality of interleukin 1 beta-converting enzyme (ICE)-like proteases as mediators of apoptosis has been suggested. The identification of the relevant substrates of the ICE protease family during apoptosis therefore constitutes a major challenge. Using human autoantibodies, we demonstrate here that a subset of autoantigens is specifically cleaved early during apoptosis. One of these cleaved molecules is identified as the catalytic subunit of the DNA-dependent protein kinase. The time courses of all proteolytic cleavages are identical and coincide with the onset of morphologic apoptosis. Furthermore, all cleavages share the same inhibition characteristics, which implicate an ICE-like activity(ies). We propose that cleavage of these autoantigens targets these molecules for an autoimmune response by revealing immunocryptic fragments in a proimmune apoptotic setting. Study of the immunogenicity of these fragments may yield insights into the autoimmune targeting of molecules. Moreover, the autoantibodies described will be valuable tools for the elucidation of mechanistically important proteolytic steps along the apoptotic pathway. |
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Authors:
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L A Casciola-Rosen; G J Anhalt; A Rosen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of experimental medicine Volume: 182 ISSN: 0022-1007 ISO Abbreviation: J. Exp. Med. Publication Date: 1995 Dec |
Date Detail:
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Created Date: 1996-01-17 Completed Date: 1996-01-17 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 2985109R Medline TA: J Exp Med Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1625-34 Citation Subset: IM |
Affiliation:
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Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Apoptosis* Autoantigens / metabolism* Caspase 1 Cell Nucleus / metabolism Cysteine Endopeptidases / metabolism DNA-Activated Protein Kinase DNA-Binding Proteins* Hela Cells / radiation effects Humans Molecular Sequence Data Molecular Weight Nuclear Proteins Peptides / metabolism Poly(ADP-ribose) Polymerases / metabolism* Protein-Serine-Threonine Kinases / metabolism* Ultraviolet Rays |
| Grant Support | |
ID/Acronym/Agency:
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AR-32490/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Autoantigens; 0/DNA-Binding Proteins; 0/Nuclear Proteins; 0/Peptides; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.7.1.37/PRKDC protein, human; EC 2.7.11.1/DNA-Activated Protein Kinase; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.22.36/Caspase 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
| Full Text | |
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Journal Information Journal ID (nlm-ta): J Exp Med ISSN: 0022-1007 ISSN: 1540-9538 Publisher: The Rockefeller University Press |
Article Information Download PDF  Print publication date: Day: 1 Month: 12 Year: 1995 Volume: 182 Issue: 6 First Page: 1625 Last Page: 1634 ID: 2192237 Publisher Id: 96096436 PubMed Id: 7500007 |
| DNA-dependent protein kinase is one of a subset of autoantigens specifically cleaved early during apoptosis | |
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