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 
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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Metadaten
Author:Nina-Naomi Kreis, Alexandra Friemel, Brigitte Zimmer, Susanne Roth, Michael A. Rieger, Udo Rolle, Frank Louwen, Juping Yuan
URN:urn:nbn:de:hebis:30:3-458394
DOI:http://dx.doi.org/10.18632/oncotarget.10330
ISSN:1949-2553
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=27384476
Parent Title (English):Oncotarget
Publisher:Impact Journals LLC
Place of publication:[s. l.]
Document Type:Article
Language:English
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
Volume:7
Issue:31
Pagenumber:14
First Page:50215
Last Page:50228
Note:
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
HeBIS PPN:432109587
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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