p15INK4b in HDAC inhibitor‐induced growth arrest

FEBS Letters

Hitomi, Toshiaki¹  Takaoka, Yuuki¹  Sakai, Toshiyuki¹  Matsuzaki, Youichirou¹  Yokota, Tomoya¹ 

[1] Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan

关键词: p15INK4b;    HDAC inhibitor;    Trichostatin A;    Butyrate;    G1 arrest;    Promoter;    p21WAF1/Cip1;   

DOI  :  10.1016/S0014-5793(03)01186-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Histone deacetylase (HDAC) inhibitors arrest human tumor cells at the G1 phase of the cell cycle and activate the cyclin-dependent kinase inhibitor, p21^WAF1/Cip1. However, several studies have suggested the existence of a p21^WAF1/Cip1-independent molecular pathway. We report here that HDAC inhibitors, trichostatin A (TSA) and sodium butyrate, activate the p15^INK4b gene, a member of the INK4 gene family, through its promoter in HaCaT cells. Furthermore, we show that up-regulation of p15^INK4b by TSA is associated with cell growth inhibition of HCT116 p21 (−/−) cells. Our findings suggest that p15^INK4b is one of the important molecular targets of HDAC inhibitors.

【 授权许可】

Unknown