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

  • 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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Author:Nina-Naomi KreisORCiDGND, Alexandra Friemel, Brigitte Zimmer, Susanne Roth, Michael A. RiegerORCiDGND, Udo RolleORCiDGND, Frank LouwenORCiDGND, Juping YuanORCiDGND
Pubmed Id:
Parent Title (English):Oncotarget
Publisher:Impact Journals LLC
Place of publication:[s. l.]
Document Type:Article
Year of Completion:2016
Date of first Publication:2016/06/30
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/03/13
Tag:Cdk1/cyclin B1; chromosome segregation; mitosis; p21 phosphorylation; p21 stability
Page Number:14
First Page:50215
Last Page:50228
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Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 3.0