title: BET bromodomain is a novel regulator of TAZ and its activity.
abstract: Transcriptional coactivator with PDZ-binding motif (TAZ) is a key transcriptional mediator of Hippo signaling that has been recently reported to mediate Wnt-activated transcription and serve as a component to suppress canonical Wnt/β-catenin activity. The Bromodomain and Extra-terminal domain (BET) family of proteins can recognize the acetylated lysine chain on histones and plays a critical role in transcriptional regulation. However, the mechanisms underlying transcriptional repression by the BET bromodomain are poorly understood. Here, we found that BET bromodomain inhibition upregulated TAZ protein and its transcriptional output, independent of its well-established role as a mediator of Hippo and Wnt signaling. Additionally, JQ1, a synthetic BET inhibitor, suppressed Wnt/β-catenin activity by upregulating TAZ. Although JQ1 upregulated TAZ, which is known to promote cell proliferation, it drastically suppressed the growth of colon cancer cells by inducing cell cycle arrest. Collectively, our study identified an unexpected transcriptional repression function of the BET bromodomain and a novel mechanism for TAZ upregulation.
authors.affiliation: Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Duan
authors.affiliation: Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China; Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Mao
authors.affiliation: Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Histology and Embryology, Xiangya School of Medicine, Central South University, 172 Tongzipo Road, Changsha, China.
authors.forename: Chaonan
authors.initials: C
authors.lastname: Liao
authors.affiliation: Department of Histology and Embryology, Xiangya School of Medicine, Central South University, 172 Tongzipo Road, Changsha, China.
authors.forename: Jinxing
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Anatomy and Neuroscience, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Fulian
authors.initials: F
authors.lastname: Huang
authors.affiliation: Endocrinology Division, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zehao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Yiyang Central Hospital, Yiyang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xia
authors.affiliation: Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, United States.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chang
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China. Electronic address: zihuac@outlook.com.
authors.forename: Zihua
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Histology and Embryology, Xiangya School of Medicine, Central South University, 172 Tongzipo Road, Changsha, China; Digestive Cancer Laboratory, Second Affiliated Hospital of Xinjiang Medical University, Urumqi 830063, China. Electronic address: huanghe@csu.edu.cn.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China. Electronic address: tianluny@163.com.
authors.forename: Tianlun
authors.initials: T
authors.lastname: Yang
mesh_terms: D000217:Acyltransferases; D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*; D060449:Wnt Signaling Pathway; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics; D000092468:Bromodomain Containing Proteins
chemical_list: D000217:Acyltransferases; D009687:Nuclear Proteins; D011506:Proteins; D014157:Transcription Factors; D051176:beta Catenin; C000624329:bromodomain and extra-terminal domain protein, human; D000092468:Bromodomain Containing Proteins; C108675:TAFAZZIN protein, human
keywords: Bromodomain and extra-terminal domain protein (BET); Colon cancer; TAZ; β-Catenin