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Lookup NU author(s): Professor Jane Endicott, Professor Martin NobleORCiD
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Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G1 phase of the cell cycle and stimulate the expression of genes required for G1 progression by phosphorylation of the product of the retinoblastoma gene, pRb. To elaborate the molecular pathway of CDK4 activation and substrate selection we have determined the structure of nonphosphorylated CDK4/cyclin D3. This structure of an authentic CDK/cyclin complex shows that cyclin binding may not be sufficient to drive the CDK active site toward an active conformation. Phosphorylated CDK4/cyclin D3 is active as a pRb kinase and is susceptible to inhibition by p27Kip1. Unlike CDK2/cyclin A, CDK4/cyclin D3 can be inactivated by treatment with lambda-phosphatase, implying that phosphorylated T172 is accessible to a generic phosphatase while bound to a cyclin. Taken together, these results suggest that the structural mechanism of CDK4/cyclin D3 activation differs markedly from that of previously studied CDK/cyclin complexes.
Author(s): Takaki T, Echalier A, Brown NR, Hunt T, Endicott JA, Noble MEM
Publication type: Article
Publication status: Published
Journal: Proceedings of the National Academy of Sciences
Year: 2009
Volume: 106
Issue: 11
Pages: 4171-4176
ISSN (print): 0027-8424
ISSN (electronic): 1091-6490
Publisher: National Academy of Sciences
URL: http://dx.doi.org/10.1073/pnas.0809674106
DOI: 10.1073/pnas.0809674106
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