RT Journal Article
SR Electronic
T1 Transcriptional Regulation of the <em>p16</em> Tumor Suppressor Gene
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4397
OP 4401
VO 35
IS 8
A1 YOJIRO KOTAKE
A1 MADOKA NAEMURA
A1 CHIHIRO MURASAKI
A1 YASUTOSHI INOUE
A1 HARUNA OKAMOTO
YR 2015
UL http://ar.iiarjournals.org/content/35/8/4397.abstract
AB 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.