Department of Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Key Clinical Laboratory of Henan Province, Zhengzhou, China.
Department of Neurosurgery, Peking University Third Hospital, Peking University, Beijing, China.
Mol Carcinog. 2024 Oct;63(10):1967-1979. doi: 10.1002/mc.23786. Epub 2024 Jul 17.
Glioblastoma (GBM) cells exhibit aberrant proliferative abilities and resistance to conventional therapies. However, the mechanisms underlying these malignant phenotypes are poorly understood. In this study, we identified ubiquitin-conjugating enzyme E2D1 (UBE2D1) as a crucial stimulator of GBM development. It is highly expressed in GBM and closely associated with poor prognosis in patients with GBM. UBE2D1 knockdown inhibits GBM cell growth and leads to G1 cell cycle arrest. Mechanistically, UBCH5A binds to p21 at the protein level and induces the ubiquitination and degradation of p21. This negative regulation is mediated by STUB1. Our findings are the first to identify UBE2D1 as a key driver of GBM growth and provide a potential target for improving prognosis and therapy.
胶质母细胞瘤(GBM)细胞表现出异常的增殖能力和对传统疗法的耐药性。然而,这些恶性表型的机制尚不清楚。在这项研究中,我们确定泛素结合酶 E2D1(UBE2D1)是 GBM 发展的关键刺激因子。UBE2D1 在 GBM 中高度表达,与 GBM 患者的预后不良密切相关。UBE2D1 敲低抑制 GBM 细胞生长并导致 G1 细胞周期停滞。在机制上,UBCH5A 在蛋白水平上与 p21 结合,并诱导 p21 的泛素化和降解。这种负调控是由 STUB1 介导的。我们的研究结果首次确定 UBE2D1 是 GBM 生长的关键驱动因素,并为改善预后和治疗提供了一个潜在的靶点。