Prdx5-KO Mouse

Prdx5, short for peroxiredoxin 5, is an enzyme that detoxifies reactive oxygen species. It is involved in multiple biological processes and signaling pathways, such as the DNA damage response (DDR), the thioredoxin/peroxiredoxin pathway, and the Keap1-Nrf2 signaling axis. Its role in maintaining genomic stability and in various disease-related signal transduction makes it a gene of significant biological importance. Genetic models can be crucial in understanding Prdx5's functions [1,2,4,5].

Knockdown of Prdx5 led to DNA damage, manifested by the induction of phosphorylated histone H2AX (γ-H2AX) and p53-binding protein 1 (53BP1). Prdx5 was shown to regulate DDR through polo-like kinase 1 (Plk1) mediated phosphorylation of ataxia telangiectasia mutated (ATM) kinase, increase of p53 acetylation at lysine 382, and induction of autophagy [1]. In castration-resistant prostate cancer, PRDX5 promotes AR inhibitor resistance and CRPC development, and its inhibition suppresses drug-tolerant persister (DTP) cell proliferation [2]. In tuberous sclerosis complex (TSC) mutant cells, auranofin and rapamycin reduce Prdx5 levels, making ER stress-induced cell death possible [3].

In conclusion, Prdx5 is essential in regulating DNA damage response, and its dysregulation is associated with diseases like castration-resistant prostate cancer and TSC-related neoplasia. The use of gene knockdown or knockout models in these studies has revealed its role in specific biological processes and disease conditions, providing potential therapeutic targets for these diseases.

References:

1. Agborbesong, Ewud, Zhou, Julie X, Li, Linda X, Calvet, James P, Li, Xiaogang. . Prdx5 regulates DNA damage response through autophagy-dependent Sirt2-p53 axis. In Human molecular genetics, 32, 567-579. doi:10.1093/hmg/ddac218. https://pubmed.ncbi.nlm.nih.gov/36067023/

2. Wang, Rong, Mi, Yuanyuan, Ni, Jiang, Feng, Ninghan, Chen, Yong Q. 2023. Identification of PRDX5 as A Target for The Treatment of Castration-Resistant Prostate Cancer. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2304939. doi:10.1002/advs.202304939. https://pubmed.ncbi.nlm.nih.gov/38115765/

3. Bovari-Biri, Judit, Abdelwahab, ElHusseiny Mohamed Mahmoud, Garai, Kitti, Pongracz, Judit E. 2023. Prdx5 in the Regulation of Tuberous Sclerosis Complex Mutation-Induced Signaling Mechanisms. In Cells, 12, . doi:10.3390/cells12131713. https://pubmed.ncbi.nlm.nih.gov/37443747/

4. Jiang, Hui, Song, DianZe, Zhou, Xiaoqin, Dai, Qian, Zeng, Mei. 2023. Maresin1 ameliorates MSU crystal-induced inflammation by upregulating Prdx5 expression. In Molecular medicine (Cambridge, Mass.), 29, 158. doi:10.1186/s10020-023-00756-w. https://pubmed.ncbi.nlm.nih.gov/37996809/

5. Chen, Xinming, Cao, Xiang, Xiao, Weizhang, Li, Ben, Xue, Qun. 2020. PRDX5 as a novel binding partner in Nrf2-mediated NSCLC progression under oxidative stress. In Aging, 12, 122-137. doi:10.18632/aging.102605. https://pubmed.ncbi.nlm.nih.gov/31899687/