Abstract
p193/CUL7 is an E3 ubiquitin ligase initially identified as an SV40 Large T Antigen binding protein. Expression of a dominant interfering variant of mouse p193/CUL7 (designated 1152stop) conferred resistance to MG132- and etoposide-induced apoptosis in U2OS cells. Immune precipitation/Western analyses revealed that endogenous p193/CUL7 formed a complex with Parc (a recently identified parkin-like ubiquitin ligase) and p53. Apoptosis resistance did not result from 1152stop-mediated disruption of the endogenous p193/CUL7 binding partners. Moreover, 1152stop molecule did not directly bind to endogenous p193/CUL7, Parc or p53. These data suggested a role for p193/CUL7 in the regulation of apoptosis independently of p53 and Parc activity.
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Apoptosis / drug effects*
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Cell Line
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Cullin Proteins / genetics
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Cullin Proteins / immunology
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Cullin Proteins / metabolism*
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Cytoplasm / metabolism
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DNA Topoisomerase IV / metabolism
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Drug Resistance*
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Enzyme Activation / drug effects
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Etoposide / pharmacology*
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Gene Expression / drug effects*
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Humans
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Leupeptins / pharmacology*
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Mice
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Mutation / genetics
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Proteasome Endopeptidase Complex / metabolism
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Proteasome Inhibitors
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Protein Binding
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
Substances
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Antibodies, Monoclonal
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Cul7 protein, mouse
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Cullin Proteins
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Leupeptins
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Proteasome Inhibitors
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Tumor Suppressor Protein p53
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Etoposide
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Proteasome Endopeptidase Complex
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DNA Topoisomerase IV
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benzyloxycarbonylleucyl-leucyl-leucine aldehyde