Abstract

Background Emerging evidence has implicated the multifaceted roles of TRIM proteins in glioblastoma; however, the function of TRIM4 in glioblastoma pathobiology has not been clarified. Methods The clinical significance of TRIM4 was elucidated through analysis of the TCGA and CGGA databases. Its function was achieved via cellular functional assays and the Xenograft tumor model employing lentivirus in LN-229 and T98G cells. Flow cytometry, Western blot, and qRT-PCR were used to examine the potential downstream proteins of TRIM4 during G 2 /M of Glioblastoma. The protein-protein interaction analyses, co-immunoprecipitation, protein turnover, and ubiquitination experiments were performed to elucidate the specific mechanism by which TRIM4 regulates the ubiquitination of CDK1. Molecular cloning experiments were employed to delineate the specific domains and ubiquitination patterns within the TRIM4-ABTB1-CDK1 axis. Results We discover that elevated TRIM4 expression in glioma is associated with increased tumor grade and unfavorable prognosis. The cellular functional assays and Xenograft tumor model demonstrated that TRIM4 knockdown suppresses cell growth by impeding the G 2 /M phase transition in LN-229 and T98G cells. The specific mechanism is that TRIM4 inhibits ABTB1-mediated CDK1 ubiquitination. Mechanistically, the 53–500 amino acid region of TRIM4 promotes ABTB1 degradation through the K6, K27, K29, and K33-linked ubiquitination. ABTB1, particularly the 1–214 amino acid region, functions as a tumor suppressor by interacting with CDK1 and promoting its destabilization via the formation of K27-linked ubiquitination. Conclusions TRIM4 acts as a promising prognostic predictor in glioma and plays an oncogenic role in glioblastoma. TRIM4-ABTB1-CDK1 may play an innovative therapeutic approach for glioblastoma treatment.