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Article

p27 allosterically activates cyclin-dependent kinase 4 and antagonizes palbociclib inhibition

12 Dec 2019

Abstract excerpt

The p27 protein is a canonical negative regulator of cell proliferation and acts primarily by inhibiting cyclin-dependent kinases (CDKs). Under some circumstances, p27 is associated with active CDK4, but no mechanism for activation has been described. We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). Structural and biochemical data...

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PMID: 31831640
DOI: 10.1126/science.aaw2106

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