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

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

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    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.

    Original languageEnglish
    Article number19174
    JournalScientific Reports
    Volume6
    DOIs
    Publication statusPublished - 2016 Jan 12

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    Carcinogenesis
    Neoplasms
    p53 Genes
    Threonine
    Oncogenes
    Phosphoric Monoester Hydrolases
    Serine
    Transcription Factors
    Up-Regulation
    Cell Proliferation
    Cell Line

    ASJC Scopus subject areas

    • General

    Cite this

    Asano, Y., Kawase, T., Okabe, A., Tsutsumi, S., Ichikawa, H., Tatebe, S., ... Ohki, R. (2016). IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis. Scientific Reports, 6, [19174]. https://doi.org/10.1038/srep19174

    IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis. / Asano, Yoshinori; Kawase, Tatsuya; Okabe, Atsushi; Tsutsumi, Shuichi; Ichikawa, Hitoshi; Tatebe, Satoko; Kitabayashi, Issay; Tashiro, Fumio; Namiki, Hideo; Kondo, Tadashi; Senba, Kentaro; Aburatani, Hiroyuki; Taya, Yoichi; Nakagama, Hitoshi; Ohki, Rieko.

    In: Scientific Reports, Vol. 6, 19174, 12.01.2016.

    Research output: Contribution to journalArticle

    Asano, Y, Kawase, T, Okabe, A, Tsutsumi, S, Ichikawa, H, Tatebe, S, Kitabayashi, I, Tashiro, F, Namiki, H, Kondo, T, Senba, K, Aburatani, H, Taya, Y, Nakagama, H & Ohki, R 2016, 'IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis', Scientific Reports, vol. 6, 19174. https://doi.org/10.1038/srep19174
    Asano, Yoshinori ; Kawase, Tatsuya ; Okabe, Atsushi ; Tsutsumi, Shuichi ; Ichikawa, Hitoshi ; Tatebe, Satoko ; Kitabayashi, Issay ; Tashiro, Fumio ; Namiki, Hideo ; Kondo, Tadashi ; Senba, Kentaro ; Aburatani, Hiroyuki ; Taya, Yoichi ; Nakagama, Hitoshi ; Ohki, Rieko. / IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis. In: Scientific Reports. 2016 ; Vol. 6.
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