Psmb5, also known as Proteasome 20S subunit beta 5, is a primary subunit of the proteasome, which is involved in the ubiquitin-proteasome pathway, a major protein degradation system in cells. This pathway plays a crucial role in regulating various cellular processes such as protein quality control, cell cycle progression, and immune response [3,5].

Knockdown of Psmb5 has shown diverse effects. In a Drosophila model of fragile X-associated tremor/ataxia syndrome (FXTAS), knockdown of Prosbeta5 (equivalent to PSMB5 in flies) suppressed CGG-associated neurodegeneration, and in human FMR1 premutation carriers, a variant associated with decreased Psmb5 expression was related to a delayed onset of FXTAS [2]. In hepatocellular carcinoma, silencing Psmb5 in Huh7 cells significantly suppressed cell proliferation and migration while increasing apoptosis, and also inhibited the phosphatidylinositol-3-kinase/Akt/mechanistic target of rapamycin pathway [1]. In breast cancer, knockdown of Psmb5 in MDA-MB-231 cells inhibited cell growth and migration, and in THP-1 monocytes, it promoted differentiation into M1 macrophages [4].

In conclusion, Psmb5 is essential for the proper functioning of the proteasome and thus for numerous cellular processes. Model-based research, especially loss-of-function experiments, has revealed its role in neurodegenerative diseases like FXTAS and in cancer development and immunosuppression, highlighting its potential as a biomarker and therapeutic target in these disease areas.

References:

1. Liu, Jun, Mi, Jinglin, Liu, Shiqian, Chen, Haiqiang, Jiang, Li. 2022. PSMB5 overexpression is correlated with tumor proliferation and poor prognosis in hepatocellular carcinoma. In FEBS open bio, 12, 2025-2041. doi:10.1002/2211-5463.13479. https://pubmed.ncbi.nlm.nih.gov/36062301/

2. Kong, Ha Eun, Lim, Junghwa, Linsalata, Alexander, Warren, Stephen T, Jin, Peng. 2022. Identification of PSMB5 as a genetic modifier of fragile X-associated tremor/ataxia syndrome. In Proceedings of the National Academy of Sciences of the United States of America, 119, e2118124119. doi:10.1073/pnas.2118124119. https://pubmed.ncbi.nlm.nih.gov/35617426/

3. Lv, Ying, Hu, Qian, Shi, Mingyang, Zhang, Aihua, Hu, Yong. 2020. The role of PSMB5 in sodium arsenite-induced oxidative stress in L-02 cells. In Cell stress & chaperones, 25, 533-540. doi:10.1007/s12192-020-01104-1. https://pubmed.ncbi.nlm.nih.gov/32301004/

4. Wang, Chih-Yang, Li, Chung-Yen, Hsu, Hui-Ping, Chen, Yi-Ling, Lai, Ming-Derg. 2017. PSMB5 plays a dual role in cancer development and immunosuppression. In American journal of cancer research, 7, 2103-2120. doi:. https://pubmed.ncbi.nlm.nih.gov/29218236/

5. Lai, Guangrui, Sun, Ru, Wu, Jingjing, Zhang, Bijun, Zhao, Yanyan. 2017. 20-HETE regulated PSMB5 expression via TGF-β/Smad signaling pathway. In Prostaglandins & other lipid mediators, 134, 123-130. doi:10.1016/j.prostaglandins.2017.08.005. https://pubmed.ncbi.nlm.nih.gov/28807746/