TRIM45 functions as a tumor suppressor in the brain via its E3 ligase activity by stabilizing p53 through K63-linked ubiquitination

Jindong Zhang, Chuanxia Zhang, Jun Cui, Jiayu Ou, Jing Han, Yunfei Qin, Feng Zhi, Rong Fu Wang

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Tripartite motif-containing protein 45 (TRIM45) belongs to a large family of RING-finger-containing E3 ligases, which are highly expressed in the brain. However, little is known regarding the role of TRIM45 in cancer biology, especially in human glioma. Here, we report that TRIM45 expression is significantly reduced in glioma tissue samples. Overexpression of TRIM45 suppresses proliferation and tumorigenicity in glioblastoma cells in vitro and in vivo. In addition, CRISPR/Cas9-mediated knockout of TRIM45 promotes proliferation and inhibits apoptosis in glioblastoma cells. Further mechanistic analyses show that TRIM45 interacts with and stabilizes p53. TRIM45 conjugates K63-linked polyubiquitin chain to the C-terminal six lysine residues of p53, thereby inhibiting the availability of these residues to the K48-linked polyubiquitination that targets p53 for degradation. These findings suggest that TRIM45 is a novel tumor suppressor that stabilizes and activates p53 in glioma.

Original languageEnglish (US)
Pages (from-to)e2831
JournalCell death & disease
Volume8
Issue number5
DOIs
StatePublished - May 25 2017

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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