前沿：T细胞中Ras GTP酶激活蛋白（RasGAPs）神经纤维瘤蛋白1和p120 RasGAP的共同缺失导致T细胞急性淋巴细胞白血病的发生。
Cutting Edge: Codeletion of the Ras GTPase-Activating Proteins (RasGAPs) Neurofibromin 1 and p120 RasGAP in T Cells Results in the Development of T Cell Acute Lymphoblastic Leukemia.
作者信息
Lubeck Beth A, Lapinski Philip E, Oliver Jennifer A, Ksionda Olga, Parada Luis F, Zhu Yuan, Maillard Ivan, Chiang Mark, Roose Jeroen, King Philip D
机构信息
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109;
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143;
出版信息
J Immunol. 2015 Jul 1;195(1):31-5. doi: 10.4049/jimmunol.1402639. Epub 2015 May 22.
Ras GTPase-activating proteins (RasGAPs) inhibit signal transduction initiated through the Ras small GTP-binding protein. However, which members of the RasGAP family act as negative regulators of T cell responses is not completely understood. In this study, we investigated potential roles for the RasGAPs RASA1 and neurofibromin 1 (NF1) in T cells through the generation and analysis of T cell-specific RASA1 and NF1 double-deficient mice. In contrast to mice lacking either RasGAP alone in T cells, double-deficient mice developed T cell acute lymphoblastic leukemia/lymphoma, which originated at an early point in T cell development and was dependent on activating mutations in the Notch1 gene. These findings highlight RASA1 and NF1 as cotumor suppressors in the T cell lineage.
Ras GTP酶激活蛋白（RasGAPs）抑制通过Ras小GTP结合蛋白启动的信号转导。然而，RasGAP家族的哪些成员作为T细胞反应的负调节因子尚未完全清楚。在本研究中，我们通过生成和分析T细胞特异性RASA1和NF1双缺陷小鼠，研究了RasGAPs RASA1和神经纤维瘤蛋白1（NF1）在T细胞中的潜在作用。与T细胞中单独缺乏任一RasGAP的小鼠不同，双缺陷小鼠发生了T细胞急性淋巴细胞白血病/淋巴瘤，其起源于T细胞发育的早期阶段，并且依赖于Notch1基因的激活突变。这些发现突出了RASA1和NF1作为T细胞谱系中的共同肿瘤抑制因子。
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