title: The tumor suppressor p33ING1b upregulates p16INK4a expression and induces cellular senescence.
abstract: ING1 protein is a tumor suppressor which plays significant roles in multiple cellular activities. p47(ING1a) and p33(ING1b) are major splice isoforms of ING1 and their roles in senescence need further investigations. Here we studied the functions of ING1 isoforms in cellular senescence and gene regulation, with focus on p16(INK4a). We observe that p33(ING1b) protein is the major ING1 isoform expressed in 2BS human diploid fibroblasts. Overexpression of p33(ING1b) induces cellular senescence and upregulates p16(INK4a) expression in 2BS fibroblasts. p33(ING1b) upregulates p16(INK4a) transcription. p33(ING1b) and p300 bind to the p16(INK4a) promoter. p300/CBP-specific inhibitor curcumin can reverse the induction of p16(INK4a) by p33(ING1b). These results help to better understand the function of ING1.
authors: Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China.
authors: Na
authors: N
authors: Li
authors: Qian
authors: Q
authors: Li
authors: Xiaoxiao
authors: X
authors: Cao
authors: Ganye
authors: G
authors: Zhao
authors: Lixiang
authors: L
authors: Xue
authors: Tanjun
authors: T
authors: Tong
mesh_terms: D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology*; D003474:Curcumin / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004791:Enzyme Inhibitors; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D025521:Tumor Suppressor Proteins; D050880:p300-CBP Transcription Factors; D003474:Curcumin