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YB 1 binds to and represses the p16 tumor suppressor gene
Author(s) -
Kotake Yojiro,
Ozawa Yuichi,
Harada Masanori,
Kitagawa Kyoko,
Niida Hiroyuki,
Morita Yasutaka,
Tanaka Kenji,
Suda Takafumi,
Kitagawa Masatoshi
Publication year - 2013
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12093
Subject(s) - biology , chromatin immunoprecipitation , cell growth , senescence , suppressor , microbiology and biotechnology , tumor suppressor gene , transcription factor , transfection , transcription (linguistics) , gene expression , chromatin , embryonic stem cell , cancer research , gene , promoter , carcinogenesis , genetics , linguistics , philosophy
Y box binding protein 1 ( YB 1) has multiple functions associated with drug resistance, cell proliferation and metastasis through transcriptional and translational regulation. Increased expression of YB 1 is closely related to tumor growth and aggressiveness. We showed that YB 1 protein levels were decreased through replicative and premature senescence and were correlated with increased expression levels of p16 INK4A tumor suppressor gene. Depletion of YB 1 was associated with increased levels of p16 in human and murine primary cells. Forced expression of YB 1 in mouse embryonic fibroblasts resulted in decreased expression of p16 and increased cell proliferation. Senescence‐associated expression of β‐galactosidase was repressed in YB 1‐over‐expressing cells. Chromatin immunoprecipitation assays showed that YB 1 directly associates with the p16 promoter. Taken together, all our findings indicate that YB 1 directly binds to and represses p16 transcription, subsequently resulting in the promotion of cell growth and prevention of cellular senescence.

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