2. Academic Validation
  3. BET bromodomain is a novel regulator of TAZ and its activity

BET bromodomain is a novel regulator of TAZ and its activity

  • Biochim Biophys Acta. 2016 Dec;1859(12):1527-1537. doi: 10.1016/j.bbagrm.2016.10.001.
Qiong Duan 1,  Yi Xiao 1,  Lingyan Zhu 2,  Zhenzhen Liu 1,  Xiaoxiao Mao 3,  Zhengxiang Zhou 1,  Chaonan Liao 4,  Jinxing Cai 4,  Fulian Huang 5,  Zehao Liu 6,  Jian Zeng 7,  Ke Xia 1,  Cheng Chang 8,  Jun Qi 9,  Zihua Chen 10,  He Huang 11,  Tianlun Yang 12
Affiliations

Affiliations

  • 1 Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China.
  • 2 Department of Endocrinology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 3 Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China; Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
  • 4 Department of Histology and Embryology, Xiangya School of Medicine, Central South University, 172 Tongzipo Road, Changsha, China.
  • 5 Department of Anatomy and Neuroscience, Xiangya School of Medicine, Central South University, Changsha, China.
  • 6 Endocrinology Division, Xiangya Hospital, Central South University, Changsha, China.
  • 7 Department of Thoracic Surgery, Yiyang Central Hospital, Yiyang, China.
  • 8 Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, United States.
  • 9 Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, United States.
  • 10 Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China. Electronic address: [email protected].
  • 11 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: [email protected].
  • 12 Cardiovascular Division, Xiangya Hospital, Central South University, Changsha, China. Electronic address: [email protected].
PMID: 27717711 DOI: 10.1016/j.bbagrm.2016.10.001
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.

Keywords

Bromodomain and extra-terminal domain protein (BET); Colon cancer; TAZ; β-Catenin.

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