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Nova Southeastern University

Chemistry and Physics Faculty Articles

2008

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Full-Text Articles in Life Sciences

Phosphorylation Of P27kip1 Regulates Assembly And Activation Of Cyclin D1-Cdk4, Michelle D. Larrea, Jiyong Liang, Thiago G. Da Silva, Feng Hong, Shan H. Shao, Kathy Han, D. Dumont, Joyce M. Slingerland Oct 2008

Phosphorylation Of P27kip1 Regulates Assembly And Activation Of Cyclin D1-Cdk4, Michelle D. Larrea, Jiyong Liang, Thiago G. Da Silva, Feng Hong, Shan H. Shao, Kathy Han, D. Dumont, Joyce M. Slingerland

Chemistry and Physics Faculty Articles

p27 mediates Cdk2 inhibition and is also found in cyclin D1-Cdk4 complexes. The present data support a role for p27 in the assembly of D-type cyclin-Cdk complexes and indicate that both cyclin D1-Cdk4-p27 assembly and kinase activation are regulated by p27 phosphorylation. Prior work showed that p27 can be phosphorylated by protein kinase B/Akt (PKB/Akt) at T157 and T198. Here we show that PKB activation and the appearance of p27pT157 and p27pT198 precede p27-cyclin D1-Cdk4 assembly in early G1. PI3K/PKB inhibition rapidly reduced p27pT157 and p27pT198 and dissociated cellular p27-cyclin D1-Cdk4. Mutant p27 allele products lacking phosphorylation at …