去泛素化酶：血液恶性肿瘤中的致癌活性和治疗靶点。
Deubiquitinases: Pro-oncogenic Activity and Therapeutic Targeting in Blood Malignancies.
机构信息
Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, 303 E. Superior Street, Chicago, IL 60611, USA.
Institute for Cancer Genetics, Department of Pathology and Cell Biology, and Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
出版信息
Trends Immunol. 2020 Apr;41(4):327-340. doi: 10.1016/j.it.2020.02.004. Epub 2020 Mar 2.
Abstract
Deubiquitinases are enzymes that remove ubiquitin moieties from the vast majority of cellular proteins, controlling their stability, interactions, and localization. The expression and activity of deubiquitinases are critical for physiology and can go awry in various diseases, including cancer. Based on recent findings in human blood cancers, we discuss the functions of selected deubiquitinases in acute leukemia and efforts to target these enzymes with the aim of blocking leukemia growth and improving disease outcomes. We focus on the emergence of the newest generation of preclinical inhibitors by discussing their modes of inhibition and their effects on leukemia biology.
摘要
去泛素化酶是一类从绝大多数细胞蛋白上去除泛素基团的酶，控制着这些蛋白的稳定性、相互作用和定位。去泛素化酶的表达和活性对生理功能至关重要，在包括癌症在内的各种疾病中可能会出现异常。基于人类血液癌症的最新发现，我们讨论了选定的去泛素化酶在急性白血病中的功能，以及用这些酶作为靶点的努力，以阻断白血病的生长并改善疾病预后。我们通过讨论其抑制模式及其对白血病生物学的影响，重点介绍新一代的临床前抑制剂的出现。
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