TY - JOUR T1 - Transcriptional Regulation of the <em>p16</em> Tumor Suppressor Gene JF - Anticancer Research JO - Anticancer Res SP - 4397 LP - 4401 VL - 35 IS - 8 AU - YOJIRO KOTAKE AU - MADOKA NAEMURA AU - CHIHIRO MURASAKI AU - YASUTOSHI INOUE AU - HARUNA OKAMOTO Y1 - 2015/08/01 UR - http://ar.iiarjournals.org/content/35/8/4397.abstract N2 - The p16 tumor suppressor gene encodes a specific inhibitor of cyclin-dependent kinase (CDK) 4 and 6 and is found altered in a wide range of human cancers. p16 plays a pivotal role in tumor suppressor networks through inducing cellular senescence that acts as a barrier to cellular transformation by oncogenic signals. p16 protein is relatively stable and its expression is primary regulated by transcriptional control. Polycomb group (PcG) proteins associate with the p16 locus in a long non-coding RNA, ANRIL-dependent manner, leading to repression of p16 transcription. YB1, a transcription factor, also represses the p16 transcription through direct association with its promoter region. Conversely, the transcription factors Ets1/2 and histone H3K4 methyltransferase MLL1 directly bind to the p16 locus and mediate p16 induction during replicative and premature senescence. In the present review, we discuss the molecular mechanisms by which these factors regulate p16 transcription. ER -