TRIM29 promotes glioblastoma progression via ubiquitinating NEFL and activating the PI3K/AKT signaling pathway

Tripartite motif-containing protein 29 (TRIM29) is a regulator of tumor progression across multiple cancer types. However, its functional significance in glioblastoma (GBM) remains poorly defined. In this study, we investigated the biological roles of TRIM29 in GBM and elucidated its underlying molecular mechanisms. Clinically, TRIM29 expression was significantly upregulated in glioma tissues compared to adjacent normal brain tissues, and elevated TRIM29 levels correlated with unfavorable prognosis in GBM patients. Functionally, both in vitro (GBM cell lines) and in vivo (a mouse xenograft model) experiments demonstrated that TRIM29 overexpression robustly enhanced GBM cell proliferation, migration, and invasive capacity. Mechanistically, TRIM29 directly interacted with neurofilament light polypeptide (NEFL), triggering K48-linked polyubiquitination and subsequent proteasomal degradation of NEFL[1]. This ubiquitination-dependent NEFL downregulation led to constitutive activation of the PI3K/AKT signaling pathway. Our findings uncover a novel TRIM29-NEFL-PI3K/AKT axis that drives glioblastoma malignancy, highlighting the therapeutic potential of targeting this pathway for GBM treatment.