title: Mitotic p21Cip1/CDKN1A is regulated by cyclin-dependent kinase 1 phosphorylation.
abstract: The multifunctional protein p21Cip1/CDKN1A (p21) is an important and universal Cdk-interacting protein. Recently, we have reported that p21 is involved in the regulation of the mitotic kinase Cdk1/cyclin B1 and critical for successful mitosis and cytokinesis. In the present work we show that S130 of p21 is phosphorylated by Cdk1/cyclin B1 during mitosis, which reduces p21's stability and binding affinity to Cdk1/cyclin B1. Interfering with this phosphorylation results in extended mitotic duration and defective chromosome segregation, indicating that this regulation ensures proper mitotic progression. Given that p53, the major transcriptional activator of p21, is the most frequently mutated gene in human cancer and that deregulated Cdk1 associates with the development of different types of cancer, this work provides new insight into the understanding of how deregulated p21 contributes to chromosomal instability and oncogenesis.
authors.affiliation: Department of Gynecology and Obstetrics, J. W. Goethe-University, D-60590 Frankfurt, Germany.
authors.forename: Nina-Naomi
authors.initials: NN
authors.lastname: Kreis
authors.affiliation: Department of Gynecology and Obstetrics, J. W. Goethe-University, D-60590 Frankfurt, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Friemel
authors.affiliation: Department of Gynecology and Obstetrics, J. W. Goethe-University, D-60590 Frankfurt, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Zimmer
authors.affiliation: Department of Gynecology and Obstetrics, J. W. Goethe-University, D-60590 Frankfurt, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Roth
authors.affiliation: Department of Hematology/Oncology, J. W. Goethe-University, D-60590 Frankfurt, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rieger
authors.affiliation: Department of Pediatric Surgery and Pediatric Urology, School of Medicine, J. W. Goethe-University, D-60590 Frankfurt, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Rolle
authors.affiliation: Department of Gynecology and Obstetrics, J. W. Goethe-University, D-60590 Frankfurt, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Louwen
authors.affiliation: Department of Gynecology and Obstetrics, J. W. Goethe-University, D-60590 Frankfurt, Germany.
authors.forename: Juping
authors.initials: J
authors.lastname: Yuan
mesh_terms: D016203:CDC2 Protein Kinase / Q000378:metabolism*; D063646:Carcinogenesis; D043171:Chromosomal Instability; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008938:Mitosis; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011994:Recombinant Proteins; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human
keywords: Cdk1/cyclin B1; chromosome segregation; mitosis; p21 phosphorylation; p21 stability