ヨゴサワ　シンゴ   YOGOSAWA Shingo   与五沢　真吾    所属   埼玉医科大学  保健医療学部 臨床検査学科    職種   准教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読あり
表題	Oct-1 is involved in the transcriptional repression of the p15(INK4b) gene
掲載誌名	正式名：FEBS LETTERS ISSNコード：0014-5793
出版社	ELSEVIER SCIENCE BV
巻・号・頁	581(6),1087-1092頁
著者・共著者	Toshiaki Hitomi,Youichirou Matsuzaki,Shusuke Yasuda,Mayumi Kawanaka,Shingo Yogosawa,Makoto Koyama,Dean Tantin,Toshiyuki Sakai
発行年月	2007/03
概要	p15(INK4b) functions as a tumor suppressor and implicated in cellular senescence. Here, we show that the Oct-1 binding site in the human p15(INK4b) gene promoter functions as a silencer. Oct-1 specifically interacts with this binding site in vitro and in vivo and SMRT and HDAC 1 are present in the p15(INK4b) proximal promoter region. Moreover, mouse embryo fibroblasts (MEFs) lacking Oct-1 have shown significantly increased levels of p15(INK4b) protein compared to their normal counterparts. Treatment with a histone deacetylase (HDAC) inhibitor has activated the expression of p15(INK4b) in wild-type MEFs but has no effect in MEFs lacking Oct-1, suggesting that Oct-1 represses p15(INK4b) gene expression in an HDAC-dependent manner. Finally, we show that the expression of Oct-1 protein significantly decreases, whereas p15(INK4b) protein significantly increases with the cellular aging process. Taken together, these results suggest that Oct-1 is an important transcriptional repressor for p15(INK4b) gene and the transcriptional repression of the p15(INK4b) gene by Oct-1 may be one of the regulatory mechanisms of cellular senescence. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
DOI	10.1016/j.febslet.2007.01.092
PMID	17316622