徐州医科大学Ren-Xian Tang团队近期取得重要工作进展，他们研究提出，LASP1和SYVN1介导的GLUD1抑制有助于乙型肝炎病毒X蛋白诱导的肝癌发生。相关研究成果2024年4月8日在线发表于《分子细胞生物学杂志》上。

据介绍，谷氨酸脱氢酶1（GLUD1）与肿瘤发生有关。然而，人们对GLUD1与肝细胞癌（HCC）之间的关系知之甚少。

研究人员证明了GLUD1在肿瘤中的表达水平显著降低，这与HCC的不良预后有关。在功能上，GLUD1沉默增强了HCC细胞的生长和迁移。从机制上讲，白细胞介素-32通过AKT激活的上调有助于GLUT1沉默促进肝癌的发生。GLUT1与AKT之间的相互作用，以及由GLUT1调节的α-酮戊二酸可以抑制AKT的激活。

此外，LIM和SH3蛋白1（LASP1）与GLUD1相互作用，并通过泛素-蛋白酶体途径诱导GLUD1降解，该途径依赖于E3泛素连接酶滑膜炎蛋白（SYVN1），LASP1增强了其与GLUT1的相互作用。在乙型肝炎病毒（HBV）相关的HCC中，HBV X蛋白（HBX）可以在LASP1和SYVN1的参与下抑制GLUT1。

总之，这一研究表明，GLUD1的沉默与HCC的发展显著相关，LASP1和SYVN1介导了GLUD1在HCC中的抑制作用，尤其是在HBV相关肿瘤中。

附：英文原文

Title: Inhibition of GLUD1 mediated by LASP1 and SYVN1 contributes to hepatitis B virus X protein-induced hepatocarcinogenesis

Author: You, Hong-Juan, Li, Qi, Ma, Li-Hong, Wang, Xing, Zhang, Huan-Yang, Wang, Yu-Xin, Bao, En-Si, Zhong, Yu-Jie, Kong, De-Long, Liu, Xiang-Ye, Kong, Fan-Yun, Zheng, Kui-Yang, Tang, Ren-Xian

Issue&Volume: 2024-04-08

Abstract: Glutamate dehydrogenase 1 (GLUD1) is implicated in oncogenesis. However, little is known about the relationship between GLUD1 and hepatocellular carcinoma (HCC). In the present study, we demonstrated that the expression levels of GLUD1 significantly decreased in tumors, which was relevant to the poor prognosis of HCC. Functionally, GLUD1 silencing enhanced the growth and migration of HCC cells. Mechanistically, the upregulation of interleukin-32 through AKT activation contributes to GLUD1 silencing-facilitated hepatocarcinogenesis. The interaction between GLUD1 and AKT, as well as α-ketoglutarate regulated by GLUD1, can suppress AKT activation. In addition, LIM and SH3 protein 1 (LASP1) interacts with GLUD1 and induces GLUD1 degradation via the ubiquitin–proteasome pathway, which relies on the E3 ubiquitin ligase synoviolin (SYVN1), whose interaction with GLUD1 is enhanced by LASP1. In hepatitis B virus (HBV)-related HCC, the HBV X protein (HBX) can suppress GLUD1 with the participation of LASP1 and SYVN1. Collectively, our data suggest that GLUD1 silencing is significantly associated with HCC development, and LASP1 and SYVN1 mediate the inhibition of GLUD1 in HCC, especially in HBV-related tumors.

DOI: 10.1093/jmcb/mjae014

Source: https://dx.doi.org/10.1093/jmcb/mjae014