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

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

  • Sci Rep. 2016 Jan 12;6:19174. doi: 10.1038/srep19174.
Yoshinori Asano 1 2,  Tatsuya Kawase 3 4,  Atsushi Okabe 5,  Shuichi Tsutsumi 5,  Hitoshi Ichikawa 6,  Satoko Tatebe 4,  Issay Kitabayashi 7,  Fumio Tashiro 4,  Hideo Namiki 2,  Tadashi Kondo 1,  Kentaro Semba 2,  Hiroyuki Aburatani 5,  Yoichi Taya 3,  Hitoshi Nakagama 8,  Rieko Ohki 1
Affiliations

Affiliations

  • 1 Division of Rare Cancer Research, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
  • 2 Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo, 169-8555, Japan.
  • 3 Radiobiology Division, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
  • 4 Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585, Japan.
  • 5 Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.
  • 6 Department of Clinical Genomics, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
  • 7 Division of Hematological Malignancy, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
  • 8 Division of Cancer Development System, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
PMID: 26754925 DOI: 10.1038/srep19174
Abstract

The transcription factors HSF1 and p53 both modulate the stress response, thereby protecting and facilitating the recovery of stressed cells, but both have the potential to promote tumor development. Here we show that a p53 target gene, IER5, encodes an activator of HSF1. IER5 forms a ternary complex with HSF1 and the Phosphatase PP2A, and promotes the dephosphorylation of HSF1 at numbers of serine and threonine residues, generating a novel, hypo-phosphorylated active form of HSF1. IER5 is also transcriptionally upregulated in various cancers, although this upregulation is not always p53-dependent. The IER5 locus is associated with a so-called super enhancer, frequently associated with hyperactivated oncogenes in Cancer cell lines. Enhanced expression of IER5 induces abnormal HSF1 activation in Cancer cells and contributes to the proliferation of these cells under stressed conditions. These results reveal the existence of a novel IER5-mediated Cancer regulation pathway that is responsible for the activation of HSF1 observed in various cancers.

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