Abstract
Misregulation of the Wnt pathway is a common route to cancer, including primary breast cancers. In this issue of Genes & Development, Miranda-Carboni and colleagues (3121-3134) demonstrate that the cyclin-dependent kinase inhibitor p27(Kip1) is ubiquitylated for proteasomal degradation in Wnt10b-induced mammary tumors exclusively by the Cul4A E3 ligase, which is strongly induced by Wnt signaling. The discovery of a new Wnt-induced proteolytic targeting system has important implications for the mechanism of Wnt-initiated tumorigenesis.
Publication types
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Comment
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cullin Proteins / genetics
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Cullin Proteins / metabolism
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Cyclin-Dependent Kinase Inhibitor p27 / genetics
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Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
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Humans
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Mice
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Neoplasms / genetics
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Neoplasms / metabolism
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Proteasome Endopeptidase Complex / metabolism
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S-Phase Kinase-Associated Proteins / genetics
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S-Phase Kinase-Associated Proteins / metabolism*
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Signal Transduction / genetics
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Signal Transduction / physiology
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Wnt Proteins / genetics
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Wnt Proteins / metabolism*
Substances
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CUL4A protein, human
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Cullin Proteins
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S-Phase Kinase-Associated Proteins
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Wnt Proteins
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Wnt10b protein, mouse
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Cyclin-Dependent Kinase Inhibitor p27
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Proteasome Endopeptidase Complex