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| Research progress on proteasome subunits in regulating occurrence and development of hepatocellular carcinoma |
HU Jingyi( ),WANG Qingqing,LIU Yang() |
| Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China |
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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 of HCC.
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Received: 11 January 2021
Published: 16 August 2021
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Corresponding Authors:
LIU Yang
E-mail: hjy558@zju.edu.cn;liuyang0620@zju.edu.cn
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蛋白酶体亚基对肝细胞癌发生发展的调控作用研究进展
蛋白酶体是真核细胞中负责降解细胞内短寿命蛋白、参与维持细胞内蛋白质稳态的重要细胞器。研究表明，在肝细胞癌（HCC）的发生发展进程中，蛋白酶体调节颗粒亚基可通过调节PTEN基因、P53、Bcl-2、Bcl-2相互作用的细胞死亡介体蛋白、周期蛋白依赖性激酶4、β型转化生长因子受体、E2F1、生长因子受体结合蛋白2等多种肿瘤相关蛋白以及相关的通路分子，例如信号转导及转录激活蛋白3、蛋白激酶B，诱使这些蛋白质功能失调，进而促进HCC的发生，癌细胞增殖、侵袭与转移。蛋白酶体核心颗粒亚基则更多参与HCC相关蛋白的降解，因此核心颗粒的抑制剂表现出良好的抗肿瘤效应。本文就当前蛋白酶体调节颗粒亚基和核心颗粒亚基在HCC发生发展过程中的调控作用及其机制进行综述。
关键词：
蛋白酶体,
蛋白酶体调节颗粒,
蛋白酶体核心颗粒,
肝细胞癌,
机制,
综述
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