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J Zhejiang Univ (Med Sci)  2021, Vol. 50 Issue (3): 396-402    DOI: 10.3724/zdxbyxb-2021-0146
    
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.



Key wordsProteasome      Proteasome regulatory particle      Proteasome core particle      Hepatocellular carcinoma      Mechanism      Review     
Received: 11 January 2021      Published: 16 August 2021
CLC:  R735.7  
Corresponding Authors: LIU Yang     E-mail: hjy558@zju.edu.cn;liuyang0620@zju.edu.cn
Cite this article:

HU Jingyi,WANG Qingqing,LIU Yang. Research progress on proteasome subunits in regulating occurrence and development of hepatocellular carcinoma. J Zhejiang Univ (Med Sci), 2021, 50(3): 396-402.

URL:

http://www.zjujournals.com/med/10.3724/zdxbyxb-2021-0146     OR     http://www.zjujournals.com/med/Y2021/V50/I3/396


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 
Figure 1 Mechanisms of proteasome regulatory particles subunits in HCC
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