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蛋白酶体亚基在调控肝细胞癌发生发展中的研究进展。

Research progress on proteasome subunits in regulating occurrence and development of hepatocellular carcinoma.

机构信息

Institute of Immunology.

出版信息

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2021 Jun 25;50(3):396-402. doi: 10.3724/zdxbyxb-2021-0146.

Abstract

Proteasome is the eukaryotic organelle responsible for degradation of short-lived proteins and involved in maintaining cellular protein homeostasis. It has been reported that during the occurrence and development of hepatocellular carcinoma (HCC), the regulatory particle subunits of proteasome regulate a series of tumor-related proteins, and proliferation, survival-associated signaling molecules, including PTEN gene, P53, Bcl-2, Bcl-2 interacting mediator of cell death (Bim), cyclin-dependent kinase 4(CDK4), transforming growth factor β receptor (TGFBR), E2F1, growth factor receptor-bound protein 2 (GRB2) . Meanwhile, these subunits regulate some tumor-associated pathway protein, such as signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT), inducing their malfunction to promote the occurrence, proliferation, invasion and metastasis of HCC. The core particle subunits are more to perform the degradation of HCC-related proteins, so inhibitors targeting the core particle show a good anti-tumor effect. This review summarizes the current research progress on the regulation and mechanism of proteasome subunits in promoting the occurrence and development .

摘要

蛋白酶体是负责降解短寿命蛋白质的真核细胞器,参与维持细胞蛋白质的内稳态。据报道,在肝细胞癌(HCC)的发生和发展过程中,蛋白酶体的调节颗粒亚基调节一系列与肿瘤相关的蛋白质,包括 PTEN 基因、P53、Bcl-2、Bcl-2 相互作用的细胞死亡介体(Bim)、细胞周期蛋白依赖性激酶 4(CDK4)、转化生长因子β受体(TGFBR)、E2F1、生长因子受体结合蛋白 2(GRB2)。同时,这些亚基调节一些与肿瘤相关的通路蛋白,如信号转导和转录激活因子 3(STAT3)和蛋白激酶 B(AKT),导致它们功能失调,从而促进 HCC 的发生、增殖、侵袭和转移。核心颗粒亚基更能执行 HCC 相关蛋白的降解,因此针对核心颗粒的抑制剂表现出良好的抗肿瘤作用。本文综述了蛋白酶体亚基在促进 HCC 发生和发展中的调节作用及其机制的研究进展。

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