Trichostatin A activates p18INK4c gene: differential activation and cooperation with p19INK4d gene.
We have reported that histone deacetylase (HDAC) inhibitors activate a member of the INK4 family, the p19INK4d gene, causing G1 phase arrest. We report here that HDAC inhibitor, Trichostatin A, activates another member of the INK4 family, the p18INK4c gene, through its promoter in Jurkat cells. Interestingly, the activation patterns of the p18INK4c gene were different from those of p19INK4d. Furthermore, mouse embryo fibroblasts lacking p18Ink4c or p18Ink4c/p19Ink4d were resistant to the growth inhibitory effects of TSA as compared to their wild-type counterpart. Our findings suggest that p18INK4c is involved in TSA-mediated cell growth inhibition and cooperates with p19INK4d.
Yokota
Tomoya
T
Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Matsuzaki
Youichirou
Y
Sakai
Toshiyuki
T
D018797:Cell Cycle Proteins / Q000235:genetics*; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050764:Cyclin-Dependent Kinase Inhibitor p19; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C493971:CDKN2C protein, human; C493974:CDKN2D protein, human; D018797:Cell Cycle Proteins; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050764:Cyclin-Dependent Kinase Inhibitor p19; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C012589:trichostatin A