Ontology highlight
ABSTRACT:
SUBMITTER: Guiley KZ
PROVIDER: S-EPMC7592119 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Guiley Keelan Z KZ Stevenson Jack W JW Lou Kevin K Barkovich Krister J KJ Kumarasamy Vishnu V Wijeratne Tilini U TU Bunch Katharine L KL Tripathi Sarvind S Knudsen Erik S ES Witkiewicz Agnieszka K AK Shokat Kevan M KM Rubin Seth M SM
Science (New York, N.Y.) 20191201 6471
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 revealed that binding of phosphorylated p27 (phosp27) to CDK4 altered the kinase adeno ...[more]