Ubiquitin C-terminal hydrolase l1 in tumorigenesis.
Ubiquitin C-terminal hydrolase l1 in tumorigenesis.
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DOI：
10.1155/2012/123706
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发表时间：
2012
影响因子：
3
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Hurst-Kennedy J;Chin LS;Li L
泛素羧基末端水解酶L1（UCH-L1，aka PGP9.5）是一种丰富的神经元去泛素化酶，也被认为具有E3泛素-蛋白连接酶活性和/或稳定体内泛素单体。最近的证据表明UCH-L1在人类癌症的发病机制和进展中的失调。虽然通常只在神经元中表达，但在许多非神经元肿瘤中发现了高水平的UCH-L1，包括乳腺癌，结肠直肠癌和胰腺癌。UCH-L1还参与了非小细胞肺癌、结直肠癌和淋巴瘤进展过程中转移和细胞生长的调节。这些研究表明，UCH-L1具有强大的致癌作用，并驱动肿瘤的发展。相反，其他人已经观察到在某些肿瘤亚型中启动子甲基化介导的UCH-L1沉默，表明UCH-L1具有潜在的肿瘤抑制作用。在本文中，我们提供了一个概述的证据支持UCH-L1参与肿瘤的发展，并讨论了UCH-L1在肿瘤发生的潜在作用机制。
Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1, aka PGP9.5) is an abundant, neuronal deubiquitinating enzyme that has also been suggested to possess E3 ubiquitin-protein ligase activity and/or stabilize ubiquitin monomers in vivo. Recent evidence implicates dysregulation of UCH-L1 in the pathogenesis and progression of human cancers. Although typically only expressed in neurons, high levels of UCH-L1 have been found in many nonneuronal tumors, including breast, colorectal, and pancreatic carcinomas. UCH-L1 has also been implicated in the regulation of metastasis and cell growth during the progression of nonsmall cell lung carcinoma, colorectal cancer, and lymphoma. Together these studies suggest UCH-L1 has a potent oncogenic role and drives tumor development. Conversely, others have observed promoter methylation-mediated silencing of UCH-L1 in certain tumor subtypes, suggesting a potential tumor suppressor role for UCH-L1. In this paper, we provide an overview of the evidence supporting the involvement of UCH-L1 in tumor development and discuss the potential mechanisms of action of UCH-L1 in oncogenesis.