1. Academic Validation
  2. TRAF4 Promotes the Proliferation of Glioblastoma by Stabilizing SETDB1 to Activate the AKT Pathway

TRAF4 Promotes the Proliferation of Glioblastoma by Stabilizing SETDB1 to Activate the AKT Pathway

  • Int J Mol Sci. 2022 Sep 5;23(17):10161. doi: 10.3390/ijms231710161.
Hongyu Gu 1 2 Shunqin Zhu 1 2 3 Cheng Peng 1 2 3 Zekun Wei 1 2 Yang Shen 1 2 Chaoyu Yuan 1 2 He Yang 1 2 Hongjuan Cui 1 2 Liqun Yang 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China.
  • 2 Cancer Center, Medical Research Institute, Southwest University, Chongqing 400715, China.
  • 3 School of Life Sciences, Southwest University, Chongqing 400715, China.
Abstract

The process of ubiquitination regulates the degradation, transport, interaction, and stabilization of substrate proteins, and is crucial for cell signal transduction and function. TNF receptor-associated factor 4, TRAF4, is a member of the TRAF family and is involved in the process of ubiquitination as an E3 ubiquitin protein Ligase. Here, we found that TRAF4 expression correlates with glioma subtype and grade, and that TRAF4 is significantly overexpressed in glioblastoma and predicts poor prognosis. Knockdown of TRAF4 significantly inhibited the growth, proliferation, migration, and invasion of glioblastoma cells. Mechanistically, we found that TRAF4 only interacts with the Tudor domain of the Akt pathway activator SETDB1. TRAF4 mediates the atypical ubiquitination of SETDB1 to maintain its stability and function, thereby promoting the activation of the Akt pathway. Restoring SETDB1 expression in TRAF4 knockdown glioblastoma cells partially restored cell growth and proliferation. Collectively, our findings reveal a novel mechanism by which TRAF4 mediates Akt pathway activation, suggesting that TRAF4 may serve as a biomarker and promising therapeutic target for glioblastoma.

Keywords

AKT; SETDB1; TRAF4; glioblastoma; ubiquitination.

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