title: Transcriptional Regulation of the p16 Tumor Suppressor Gene.
abstract: 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.
authors.affiliation: Department of Biological and Environmental Chemistry, Faculty of Humanity-Oriented Science and Engineering, Kinki University, Fukuoka, Japan ykotake@fuk.kindai.ac.jp.
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Kotake
authors.affiliation: Department of Biological and Environmental Chemistry, Faculty of Humanity-Oriented Science and Engineering, Kinki University, Fukuoka, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Naemura
authors.affiliation: Department of Biological and Environmental Chemistry, Faculty of Humanity-Oriented Science and Engineering, Kinki University, Fukuoka, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Murasaki
authors.affiliation: Department of Biological and Environmental Chemistry, Faculty of Humanity-Oriented Science and Engineering, Kinki University, Fukuoka, Japan.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Biological and Environmental Chemistry, Faculty of Humanity-Oriented Science and Engineering, Kinki University, Fukuoka, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D016922:Cellular Senescence / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D051788:Myeloid-Lymphoid Leukemia Protein / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics*; D063146:Polycomb-Group Proteins / Q000235:genetics / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D050787:Proto-Oncogene Protein c-ets-2 / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics; D014158:Transcription, Genetic; D051840:Y-Box-Binding Protein 1 / Q000235:genetics
chemical_list: C561518:CDKN2B antisense RNA, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C494041:ETS1 protein, human; C494069:ETS2 protein, human; C497422:KMT2A protein, human; D063146:Polycomb-Group Proteins; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D062085:RNA, Long Noncoding; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6
keywords: ANRIL; CDK inhibitor; Cell cycle; MLL; p16; polycomb; review; transcription