TY - JOUR
T1 - CDK inhibitors, p21Cip1 and p27Kip1, participate in cell cycle exit of mammalian cardiomyocytes
AU - Tane, Shoji
AU - Ikenishi, Aiko
AU - Okayama, Hitomi
AU - Iwamoto, Noriko
AU - Nakayama, Keiichi I.
AU - Takeuchi, Takashi
N1 - Funding Information:
The authors wish to thank Dr. Philip Leder (Harvard Medical School, Boston) for kindly providing the p21 Cip1 knockout mice. We also thank Ms. Satomi Ikuta (Tottori University, Yonago) for her technical assistance. This work was partially supported by a research Grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2014/1/17
Y1 - 2014/1/17
N2 - 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 p21Cip1 and p27Kip1 but not p57Kip2 showed a peak around postnatal day 5, when cyclin E- and cyclin A-CDK activities start to decrease. p21Cip1 and p27 Kip1 bound to cyclin E, cyclin A and CDK2 at postnatal stages. Cell cycle distribution patterns of postnatal cardiomyocytes in p21Cip1 and p27Kip1 knockout mice showed failure in the cell cycle exit at G1-phase, and endoreplication. These results indicate that p21Cip1 and p27Kip play important roles in the cell cycle exit of postnatal cardiomyocytes.
AB - 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 p21Cip1 and p27Kip1 but not p57Kip2 showed a peak around postnatal day 5, when cyclin E- and cyclin A-CDK activities start to decrease. p21Cip1 and p27 Kip1 bound to cyclin E, cyclin A and CDK2 at postnatal stages. Cell cycle distribution patterns of postnatal cardiomyocytes in p21Cip1 and p27Kip1 knockout mice showed failure in the cell cycle exit at G1-phase, and endoreplication. These results indicate that p21Cip1 and p27Kip play important roles in the cell cycle exit of postnatal cardiomyocytes.
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U2 - 10.1016/j.bbrc.2013.12.109
DO - 10.1016/j.bbrc.2013.12.109
M3 - Article
C2 - 24380855
AN - SCOPUS:84893651561
VL - 443
SP - 1105
EP - 1109
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -