Oncotarget

Research Papers:

Mitotic p21Cip1/CDKN1A is regulated by cyclin-dependent kinase 1 phosphorylation

Nina-Naomi Kreis _, Alexandra Friemel, Brigitte Zimmer, Susanne Roth, Michael A. Rieger, Udo Rolle, Frank Louwen and Juping Yuan

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Oncotarget. 2016; 7:50215-50228. https://doi.org/10.18632/oncotarget.10330

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Abstract

Nina-Naomi Kreis1, Alexandra Friemel1, Brigitte Zimmer1, Susanne Roth1, Michael A. Rieger2,3,4, Udo Rolle5, Frank Louwen1, Juping Yuan1

1Department of Gynecology and Obstetrics, J. W. Goethe-University, D-60590 Frankfurt, Germany

2Department of Hematology/Oncology, J. W. Goethe-University, D-60590 Frankfurt, Germany

3German Cancer Consortium (DKTK), Heidelberg, Germany

4German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of Pediatric Surgery and Pediatric Urology, School of Medicine, J. W. Goethe-University, D-60590 Frankfurt, Germany

Correspondence to:

Nina-Naomi Kreis, email: Nina-Naomi.Kreis@kgu.de

Juping Yuan, email: yuan@em.uni-frankfurt.de

Keywords: p21 phosphorylation, mitosis, Cdk1/cyclin B1, p21 stability, chromosome segregation

Abbreviations: Cdk1, cyclin-dependent kinase 1; Cip1, Cdk-interacting protein 1; MCAK, mitotic centromere-associated kinesin; CHX, cycloheximide

Received: March 29, 2016     Accepted: June 17, 2016     Published: June 30, 2016

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.


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