Hyper-SUMOylation of ERG Is Essential for the Progression of Acute Myeloid Leukemia.
Hyper-SUMOylation of ERG Is Essential for the Progression of Acute Myeloid Leukemia.
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ERG 的过度 SUMO 化对于急性髓系白血病的进展至关重要
DOI：
10.3389/fmolb.2021.652284
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发表时间：
2021
影响因子：
5
通讯作者：
Qi Y
中科院分区：
文献类型：
--
作者：
Chen X;Qin Y;Zhang Z;Xing Z;Wang Q;Lu W;Yuan H;Du C;Yang X;Shen Y;Zhao B;Shao H;Wang X;Wu H;Qi Y
白血病是一种以骨髓中未成熟的造血祖细胞分化停滞和恶性增殖为特征的造血组织恶性疾病。ERG(ETS相关基因)是E26转化特异性转录因子家族中的重要成员，在生理和病理过程中发挥着重要作用。然而，ERG及其修饰在白血病中的作用尚不清楚。在本研究中，我们稳定地敲除或过表达ERG在白血病细胞中，观察到ERG显著促进AML(急性髓系白血病)细胞的增殖和抑制其分化。进一步的实验表明，ERG主要被SUMO2修饰，而SUMO2被SENP2去共轭修饰。PML促进ERG的SUMO化，增强其稳定性。三氧化二砷降低ERG的表达水平，进一步促进细胞分化。此外，ERG中的相扑位点突变抑制了其促进白血病细胞增殖和抑制其分化的能力。我们的结果表明ERG SUMO化在AML的发生发展中起着至关重要的作用，为AML的临床治疗提供了强有力的靶向治疗策略。
Leukemia is a malignant disease of hematopoietic tissue characterized by the differentiation arrest and malignant proliferation of immature hematopoietic precursor cells in bone marrow. ERG (ETS-related gene) is an important member of the E26 transformation-specific (ETS) transcription factor family that plays a crucial role in physiological and pathological processes. However, the role of ERG and its modification in leukemia remains underexplored. In the present study, we stably knocked down or overexpressed ERG in leukemia cells and observed that ERG significantly promotes the proliferation and inhibits the differentiation of AML (acute myeloid leukemia) cells. Further experiments showed that ERG was primarily modified by SUMO2, which was deconjugated by SENP2. PML promotes the SUMOylation of ERG, enhancing its stability. Arsenic trioxide decreased the expression level of ERG, further promoting cell differentiation. Furthermore, the mutation of SUMO sites in ERG inhibited its ability to promote the proliferation and inhibit the differentiation of leukemia cells. Our results demonstrated the crucial role of ERG SUMOylation in the development of AML, providing powerful targeted therapeutic strategies for the clinical treatment of AML.
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