title: YAP/TEAD-mediated transcription controls cellular senescence.
abstract: Transcription coactivator Yes-associated protein (YAP) plays an important role in the regulation of cell proliferation and apoptosis. Here, we identify a new role of YAP in the regulation of cellular senescence. We find that the expression levels of YAP proteins decrease following the replication-induced cellular senescence in IMR90 cells. Silencing of YAP inhibits cell proliferation and induces premature senescence. In additional experiments, we observe that cellular senescence induced by YAP deficiency is TEAD- and Rb/p16/p53-dependent. Furthermore, we show that Cdk6 is a direct downstream target gene of YAP in the regulation of cellular senescence, and the expression of Cdk6 is through the YAP-TEAD complex. Ectopic expression of Cdk6 rescued YAP knockdown-induced senescence. Finally, we find that downregulation of YAP in tumor cells increases senescence in response to chemotherapeutic agents, and YAP or Cdk6 expression rescues cellular senescence. Taken together, our findings define the critical role of YAP in the regulation of cellular senescence and provide a novel insight into a potential chemotherapeutic avenue for tumor suppression.
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xie
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Han
authors.initials: H
authors.lastname: Feng
authors.forename: Shengyi
authors.initials: S
authors.lastname: Peng
authors.forename: Ursula
authors.initials: U
authors.lastname: Adams
authors.forename: Yujie
authors.initials: Y
authors.lastname: Bai
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.forename: Junjian
authors.initials: J
authors.lastname: Huang
authors.forename: Songshu
authors.initials: S
authors.lastname: Meng
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000235:genetics*; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D056945:Hep G2 Cells; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016160:Retinoblastoma Protein; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; C106169:TEAD3 protein, human; C486309:TEAD4 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6