文章：

去泛素化酶ATXN3通过稳定TAZ促进肝细胞癌进展

The deubiquitinating enzyme ATXN3 promotes hepatocellular carcinoma progression by stabilizing TAZ

原文发布日期：2024-12-13

英文摘要：

Hepatocellular carcinoma (HCC) was a primary cause of cancer-related morbidity and mortality in China. ATXN3 was a deubiquitinase (DUB) associated with spinocerebellar ataxia, widely expressed in the cytoplasm and nucleus of cells in the central nervous system and other tissues. The crucial role of the Hippo pathway in tumorigenesis has been established, among which TAZ served as one of the key molecules. However, the mechanisms underlying the deubiquitinase and TAZ in HCC remained largely unknown. In the present study, we explored that ATXN3 was overexpressed in HCC. ATXN3 promoted the proliferation, migration, invasion, and tumorigenic ability of HCC in vitro and in vivo. Besides, we explored that ATXN3 was positively associated with TAZ in HCC. ATXN3 could interact with, stabilize, and deubiquitylate TAZ in a deubiquitylase-dependent manner. Specifically, this interaction was primarily mediated by the C-terminal domain of TAZ and Josephin domain of ATXN3, thereby inhibiting the K48-linked ubiquitin chain on TAZ. Furthermore, we demonstrated that ATXN3 promoted the occurrence and development of HCC by regulating TAZ. Therefore, our study revealed the oncogenic function of ATXN3 and an interesting deubiquitination mechanism of ATXN3 and TAZ in HCC, providing new insights into the diagnosis and treatment of HCC. 

摘要翻译：

肝细胞癌（HCC）是中国癌症相关发病和死亡的主要原因。ATXN3是一种与脊髓小脑共济失调相关的去泛素化酶（DUB），广泛表达于中枢神经系统及其他组织细胞的细胞质和细胞核中。Hippo信号通路在肿瘤发生中的关键作用已被证实，其中TAZ是该通路的核心分子之一。然而，去泛素化酶与TAZ在HCC中的作用机制尚不明确。本研究发现在HCC中ATXN3呈现过表达现象，且能够促进HCC的体外增殖、迁移、侵袭能力及体内成瘤能力。此外，研究证实ATXN3与TAZ在HCC中呈正相关关系，并以去泛素化酶依赖的方式与TAZ相互作用，增强其稳定性并降低其泛素化水平。具体而言，这种相互作用主要由TAZ的C端结构域和ATXN3的Josephin结构域介导，从而抑制TAZ的K48连接泛素链。进一步研究证明，ATXN3通过调控TAZ促进HCC的发生发展。本研究揭示了ATXN3的致癌功能及其与TAZ在HCC中新颖的去泛素化调控机制，为HCC的诊断和治疗提供了新的见解。

原文链接：

The deubiquitinating enzyme ATXN3 promotes hepatocellular carcinoma progression by stabilizing TAZh