MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Murata, K.
Right arrow Articles by Minato, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Murata, K.
Right arrow Articles by Minato, N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2005, p. 4262-4271, Vol. 25, No. 10
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.10.4262-4271.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Hes1 Directly Controls Cell Proliferation through the Transcriptional Repression of p27Kip1

Kaoru Murata,1 Masakazu Hattori,1 Norihito Hirai,1 Yoriko Shinozuka,1 Hiromi Hirata,2 Ryoichiro Kageyama,2 Toshiyuki Sakai,3 and Nagahiro Minato1*

Department of Immunology and Cell Biology, Graduate School of Biostudies,1 Institute for Virus Research, Kyoto University, Kyoto 606-8501,2 Department of Preventive Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan3

Received 15 September 2004/ Returned for modification 18 November 2004/ Accepted 17 February 2005

A transcriptional regulator, Hes1, plays crucial roles in the control of differentiation and proliferation of neuronal, endocrine, and T-lymphocyte progenitors during development. Mechanisms for the regulation of cell proliferation by Hes1, however, remain to be verified. In embryonic carcinoma cells, endogenous Hes1 expression was repressed by retinoic acid in concord with enhanced p27Kip1 expression and cell cycle arrest. Conversely, conditional expression of a moderate but not maximal level of Hes1 in HeLa cells by a tetracycline-inducible system resulted in reduced p27Kip1 expression, which was attributed to decreased basal transcript rather than enhanced proteasomal degradation, with concomitant increases in the growth rate and saturation density. Hes1 induction repressed the promoter activity of a 5' flanking basal enhancer region of p27Kip1 gene in a manner dependent on Hes1 expression levels, and this was mediated by its binding to class C sites in the promoter region. Finally, hypoplastic fetal thymi, as well as livers and brains of Hes1-deficient mice, showed significantly increased p27Kip1 transcripts compared with those of control littermates. These results have suggested that Hes1 directly contributes to the promotion of progenitor cell proliferation through transcriptional repression of a cyclin-dependent kinase inhibitor, p27Kip1.


* Corresponding author. Mailing address: Department of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. Phone: 81-75-753-4659. Fax: 81-75-753-4403. E-mail: minato{at}imm.med.kyoto-u.ac.jp.


Molecular and Cellular Biology, May 2005, p. 4262-4271, Vol. 25, No. 10
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.10.4262-4271.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2005 by the American Society for Microbiology. All rights reserved.