TRIM25 enhances cell growth and cell survival by modulating p53 signals via interaction with G3BP2 in prostate cancer

Ken Ichi Takayama, Takashi Suzuki, Tomoaki Tanaka, Tetsuya Fujimura, Satoru Takahashi, Tomohiko Urano, Kazuhiro Ikeda, Satoshi Inoue

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Prostate cancer growth is promoted by the gene regulatory action of androgen receptor (AR) and its downstream signals. The aberrant dysfunction of tumor suppressor p53 has an important role in the prognosis of cancer. We previously found that androgen treatments translocate p53 to the cytoplasm. The mechanism of this translocation depends on sumoylation of p53 by complex of SUMO E3 ligase RanBP2 with androgen-induced GTPase-activating protein-binding protein 2 (G3BP2). Here, we identified tripartite motif-containing protein 25 (TRIM25)/estrogen-responsive finger protein (Efp) as a novel interacting partner of G3BP2 protein complex. Then, we demonstrated that TRIM25 knockdown resulted in p53 downstream activation for cell cycle inhibition and apoptosis induction in LNCaP and 22Rv1 cells. In contrast, overexpression of TRIM25 promoted prostate cancer cell proliferation and inhibited apoptosis by docetaxel treatment in LNCaP cells. We observed that p53 activity was reduced by mechanism of G3BP2-mediated nuclear export in TRIM25-overexpressing prostate cancer cells. We also found TRIM25 is important for G3BP2/RanBP2-mediated p53 modification. Clinically, we newly demonstrated that TRIM25 is a prognostic factor for prostate cancer patients. Expression of TRIM25 is significantly associated with cytoplasmic p53 expression and G3BP2. Moreover, TRIM25 knockdown results in reduced tumor growth and increased p53 activity in the mouse xenograft model of prostate cancer. Thus, our findings show that overexpression of TRIM25 promoted prostate cancer cell proliferation and cell survival by modulating p53 nuclear export mechanism with G3BP2 interaction.

Original languageEnglish
Pages (from-to)2165-2180
Number of pages16
JournalOncogene
Volume37
Issue number16
DOIs
Publication statusPublished - 2018 Apr 1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Takayama, K. I., Suzuki, T., Tanaka, T., Fujimura, T., Takahashi, S., Urano, T., Ikeda, K., & Inoue, S. (2018). TRIM25 enhances cell growth and cell survival by modulating p53 signals via interaction with G3BP2 in prostate cancer. Oncogene, 37(16), 2165-2180. https://doi.org/10.1038/s41388-017-0095-x