"IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis"

Speaker: Dr. Rieko Ohki

Group Leader, Division of Rare Cancer Research, National Cancer Center Research Institute

Title: IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis

Abstract: Both p53 and HSF1 are transcription factors involved in the stress response.  While HSF1 has long been known to function in the protection and recovery of stressed cells, the role of p53 in this response has only recently received much attention.  One question has been whether the action of p53 and HSF1 in the stress response may also promote tumor development in cancer cells.  Here we show that IER5, a p53 target gene, functions as a novel HSF1 activator within a complex consisting of IER5-HSF1-PP2A.  IER5 facilitates PP2A dephosphorylation of HSF1 within this complex, generating a novel hypo-phosphorylated form of HSF1.  IER5 is transcriptionally upregulated in various cancers; however this upregulation can occur in a p53-independent manner.  The IER5 locus has also been reported to contain a so-called super enhancer, which is associated with gene hyperactivation in various cancer cell lines.  Enhanced expression of IER5 thus induces abnormal HSF1 activation in cancer cells and contributes to survival of these cells under stressed conditions.  Our results reveal the existence of a novel IER5-mediated pathway of HSF1 activation that may be responsible for the activation of HSF1 observed in various cancers.

References:

1. Yoshinori Asano, Tatsuya Kawase, Atsushi Okabe, Shuichi Tsutsumi, Hitoshi Ichikawa, Satoko Tatebe, Issay Kitabayashi, Fumio Tashiro, Hideo Namiki, Tadashi Kondo, Kentaro Semba, Hiroyuki Aburatani, Yoichi Taya, Hitoshi Nakagama and Rieko Ohki. 

IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis.

Scientific Reports, 6, 19174; doi: 10.1038/srep19174 (2016).

Biography:

1997      Ph.D., Dept. of Biochemistry and Biophysics, Faculty of Sciences, University of Tokyo (Japan)

1997-1999   Postdoctoral Research Fellow, Department of Immunology (Professor Tadatsugu Taniguchi), Graduate School of              Medicine and Faculty of Medicine, University of Tokyo

1999-2002   Postdoctoral Research Fellow, Department of Life Science (Professor Fuyuki Ishikawa), Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology

2002-2011  Research Associate, Radiobiology Division (2002-2008), Growth Factor Division (2008-2010), Division of Cancer Biology (2010~2011), National Cancer Center Research Institute

2011-present  Group leader, Division of Refractory Cancer Research (2011-2014), Division of Rare Cancer Research(2014-), National Cancer Center Research Institute

Speciality and Present Interest:

Identification and analysis of genes involved tumorigenesis

Phone: 81-3-3542-2511 ext.4460

E-mail: rohki@ncc.go.jp