title: YB1 binds to and represses the p16 tumor suppressor gene.
abstract: Y box binding protein 1 (YB1) has multiple functions associated with drug resistance, cell proliferation and metastasis through transcriptional and translational regulation. Increased expression of YB1 is closely related to tumor growth and aggressiveness. We showed that YB1 protein levels were decreased through replicative and premature senescence and were correlated with increased expression levels of p16(INK) (4A) tumor suppressor gene. Depletion of YB1 was associated with increased levels of p16 in human and murine primary cells. Forced expression of YB1 in mouse embryonic fibroblasts resulted in decreased expression of p16 and increased cell proliferation. Senescence-associated expression of β-galactosidase was repressed in YB1-over-expressing cells. Chromatin immunoprecipitation assays showed that YB1 directly associates with the p16 promoter. Taken together, all our findings indicate that YB1 directly binds to and represses p16 transcription, subsequently resulting in the promotion of cell growth and prevention of cellular senescence.
authors.affiliation: Department of Biological and Environmental Chemistry, Faculty of Humanity-Oriented Science and Engineering, Kinki University, 11-6 Kayanomori, Iizuka, Fukuoka, 820-8555, Japan.
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Kotake
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Harada
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kitagawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Niida
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Morita
authors.forename: Kenji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kitagawa
mesh_terms: D000818:Animals; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D051840:Y-Box-Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C541744:Ybx1 protein, mouse; C070856:YBX1 protein, human