Delvecchio Vincenza Simona, Fierro Claudia, Giovannini Sara, Melino Gerry, Bernassola Francesca
Department of Experimental Medicine, TOR, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy.
Discov Oncol. 2021 Oct 8;12(1):39. doi: 10.1007/s12672-021-00435-4.
Ubiquitination-mediated proteolysis or regulation of proteins, ultimately executed by E3 ubiquitin ligases, control a wide array of cellular processes, including transcription, cell cycle, autophagy and apoptotic cell death. HECT-type E3 ubiquitin ligases can be distinguished from other subfamilies of E3 ubiquitin ligases because they have a C-terminal HECT domain that directly catalyzes the covalent attachment of ubiquitin to their substrate proteins. Deregulation of HECT-type E3-mediated ubiquitination plays a prominent role in cancer development and chemoresistance. Several members of this subfamily are indeed frequently deregulated in human cancers as a result of genetic mutations and altered expression or activity. HECT-type E3s contribute to tumorigenesis by regulating the ubiquitination rate of substrates that function as either tumour suppressors or oncogenes. While the pathological roles of the HECT family members in solid tumors are quite well established, their contribution to the pathogenesis of hematological malignancies has only recently emerged. This review aims to provide a comprehensive overview of the involvement of the HECT-type E3s in leukemogenesis.
泛素化介导的蛋白质水解或蛋白质调控最终由E3泛素连接酶执行，它控制着包括转录、细胞周期、自噬和凋亡性细胞死亡在内的一系列细胞过程。HECT型E3泛素连接酶可与E3泛素连接酶的其他亚家族区分开来，因为它们具有一个C末端HECT结构域，该结构域直接催化泛素与底物蛋白的共价连接。HECT型E3介导的泛素化失调在癌症发展和化疗耐药中起重要作用。由于基因突变以及表达或活性改变，该亚家族的几个成员在人类癌症中确实经常失调。HECT型E3通过调节作为肿瘤抑制因子或癌基因的底物的泛素化速率来促进肿瘤发生。虽然HECT家族成员在实体瘤中的病理作用已相当明确，但它们对血液系统恶性肿瘤发病机制的贡献直到最近才显现出来。本综述旨在全面概述HECT型E3在白血病发生中的作用。
