UBE2D1 promotes glioblastoma proliferation by modulating p21 ubiquitination.

IF 3 2区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Carcinogenesis Pub Date : 2024-10-01 Epub Date: 2024-07-17 DOI:10.1002/mc.23786
Yongfeng Wang, Qianquan Ma, Haoyu Li, Wei Huang, Jia You, Dian Liu
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Abstract

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.

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UBE2D1 通过调节 p21 泛素化促进胶质母细胞瘤增殖。
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抵抗力。然而,人们对这些恶性表型的机制知之甚少。在这项研究中,我们发现泛素结合酶 E2D1(UBE2D1)是 GBM 发育的关键刺激因子。它在 GBM 中高表达,与 GBM 患者的不良预后密切相关。敲除 UBE2D1 可抑制 GBM 细胞生长并导致 G1 细胞周期停滞。从机理上讲,UBCH5A 在蛋白水平上与 p21 结合,诱导 p21 泛素化和降解。这种负调控是由 STUB1 介导的。我们的发现首次确定了 UBE2D1 是 GBM 生长的关键驱动因素,并为改善预后和治疗提供了潜在靶点。
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来源期刊
Molecular Carcinogenesis
Molecular Carcinogenesis 医学-生化与分子生物学
CiteScore
7.30
自引率
2.20%
发文量
112
审稿时长
2 months
期刊介绍: Molecular Carcinogenesis publishes articles describing discoveries in basic and clinical science of the mechanisms involved in chemical-, environmental-, physical (e.g., radiation, trauma)-, infection and inflammation-associated cancer development, basic mechanisms of cancer prevention and therapy, the function of oncogenes and tumors suppressors, and the role of biomarkers for cancer risk prediction, molecular diagnosis and prognosis.
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