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https://hdl.handle.net/2440/8786
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Type: | Journal article |
Title: | DNA-dependent protein kinase catalytic subunit: a target for an ICE-like protease in apoptosis |
Author: | Song, Q. Lees-Miller, S. Kumar, S. Zhang, N. Chan, D. Smith, G. Jackson, S. Alnemri, E. Litwack, G. Khanna, K. Lavin, M. |
Citation: | The EMBO Journal, 1996; 15(13):3238-3246 |
Publisher: | OXFORD UNIV PRESS UNITED KINGDOM |
Issue Date: | 1996 |
ISSN: | 0261-4189 1460-2075 |
Statement of Responsibility: | Song, Q ; Lees-miller, S P ; Kumar, S ; Zhang, Z ; Chan, D W ; Smith, G C ; Jackson, S P ; Alnemri, E S ; Litwack, G ; Khanna, K K ; Lavin, M F |
Abstract: | Radiosensitive cell lines derived from X-ray cross complementing group 5 (XRCC5), SCID mice and a human glioma cell line lack components of the DNA-dependent protein kinase, DNA-PK, suggesting that DNA-PK plays an important role in DNA double-strand break repair. Another enzyme implicated in DNA repair, poly(ADP-ribose) polymerase, is cleaved and inactivated during apoptosis, suggesting that some DNA repair proteins may be selectively targeted for destruction during apoptosis. Here we demonstrate that DNA-PKcs, the catalytic subunit of DNA-PK, is preferentially degraded after the exposure of different cell types to a variety of agents known to cause apoptosis. However, Ku, the DNA-binding component of the enzyme, remains intact. Degradation of DNA-PKcs was accompanied by loss of DNA-PK activity. One cell line resistant to etoposide-induced apoptosis failed to show degradation of DNA-PKcs. Protease inhibitor data implicated an ICE-like protease in the cleavage of DNA-PKcs, and it was subsequently shown that the cysteine protease CPP32, but not Mch2alpha, ICE or TX, cleaved purified DNA-PKcs into three fragments of comparable size with those observed in cells undergoing apoptosis. Cleavage sites in DNA-PKcs, determined by antibody mapping and microsequencing, were shown to be the same for CPP32 cleavage and for cleavage catalyzed by extracts from cells undergoing apoptosis. These observations suggest that DNA-PKcs is a critical target for proteolysis by an ICE-like protease during apoptosis. |
Keywords: | Cell Line Hela Cells Tumor Cells, Cultured Animals Humans Mice Mice, SCID Etoposide Cysteine Endopeptidases Caspase 1 DNA-Binding Proteins Nuclear Proteins DNA Primers Antibodies Apoptosis Base Sequence Substrate Specificity Hydrolysis Catalysis Molecular Sequence Data DNA-Activated Protein Kinase Protein Serine-Threonine Kinases |
DOI: | 10.1002/j.1460-2075.1996.tb00688.x |
Published version: | http://dx.doi.org/10.1002/j.1460-2075.1996.tb00688.x |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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