Abstract
The evolutionarily conserved protein COP1 has been shown to operate as an E3 ubiquitin ligase complex, and a number of putative substrates have been identified, including the c-JUN oncoprotein and p53 tumor suppressor protein. New work by Migliorini and colleagues described in the current issue of JCI demonstrates that COP1 acts as a tumor suppressor in vivo and does so, at least in part, by promoting the destruction of c-JUN. These findings challenge the view that COP1 regulates p53 stability and call into question the wisdom of developing COP1 inhibitors as potential anticancer agents.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Comment
MeSH terms
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Animals
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Enzyme Stability
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Humans
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JNK Mitogen-Activated Protein Kinases / metabolism
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Mice
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Mice, Mutant Strains
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Models, Biological
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Neoplasms / etiology
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Tumor Suppressor Protein p53 / metabolism
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism*
Substances
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Nuclear Proteins
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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COP1 protein, mouse
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Ubiquitin-Protein Ligases
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JNK Mitogen-Activated Protein Kinases