Format

Send to

Choose Destination
See comment in PubMed Commons below
Biochem Biophys Res Commun. 2014 Jan 17;443(3):1105-9. doi: 10.1016/j.bbrc.2013.12.109. Epub 2013 Dec 28.

CDK inhibitors, p21(Cip1) and p27(Kip1), participate in cell cycle exit of mammalian cardiomyocytes.

Author information

1
School of Life Sciences, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan.
2
Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
3
School of Life Sciences, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan. Electronic address: takeuchi@med.tottori-u.ac.jp.

Abstract

Mammalian cardiomyocytes actively proliferate during embryonic stages, following which cardiomyocytes exit their cell cycle after birth. The irreversible cell cycle exit inhibits cardiac regeneration by the proliferation of pre-existing cardiomyocytes. Exactly how the cell cycle exit occurs remains largely unknown. Previously, we showed that cyclin E- and cyclin A-CDK activities are inhibited before the CDKs levels decrease in postnatal stages. This result suggests that factors such as CDK inhibitors (CKIs) inhibit CDK activities, and contribute to the cell cycle exit. In the present study, we focused on a Cip/Kip family, which can inhibit cyclin E- and cyclin A-CDK activities. Expression of p21(Cip1) and p27(Kip1) but not p57(Kip2) showed a peak around postnatal day 5, when cyclin E- and cyclin A-CDK activities start to decrease. p21(Cip1) and p27(Kip1) bound to cyclin E, cyclin A and CDK2 at postnatal stages. Cell cycle distribution patterns of postnatal cardiomyocytes in p21(Cip1) and p27(Kip1) knockout mice showed failure in the cell cycle exit at G1-phase, and endoreplication. These results indicate that p21(Cip1) and p27(Kip) play important roles in the cell cycle exit of postnatal cardiomyocytes.

KEYWORDS:

CDK; CDK inhibitor; CKI; CM; Cardiomyocyte; Cell cycle exit; KO; Mouse; cardiomyocyte; cyclin dependent kinase; cyclin dependent kinase inhibitor; knockout

PMID:
24380855
DOI:
10.1016/j.bbrc.2013.12.109
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center