Good COP1 or bad COP1? In vivo veritas
Wenyi Wei, William G. Kaelin Jr.
Wenyi Wei, William G. Kaelin Jr.
Published March 14, 2011
Citation Information: J Clin Invest. 2011;121(4):1263-1265. https://doi.org/10.1172/JCI57080.
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Commentary

Good COP1 or bad COP1? In vivo veritas

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.

Authors

Wenyi Wei, William G. Kaelin Jr.

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Figure 1

COP1 functions as an E3 ubiquitin ligase.

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COP1 functions as an E3 ubiquitin ligase. Both p53 and c-JUN have been i...
Both p53 and c-JUN have been identified as potential COP1 substrates. Theoretically, COP1 could act as an oncoprotein by promoting the destruction of the p53 tumor suppressor (A; Model I) or as a tumor suppressor protein by promoting the destruction of c-JUN (B; Model II). Data provided in the current issue of JCI by Migliorini et al., obtained using genetically engineered mice, strongly favor Model II.