Plk3-KO Mouse

Plk3, a member of the polo-like kinases (Plks) family, is a highly conserved serine/threonine kinase in eukaryotes. Plks play key roles in cell cycle regulation, especially in the G1, S, and G2 phases [2]. Plk3 contributes to the control and progression of the cell cycle, acts as a mediator of apoptosis and responds to various cellular stresses [4].

In breast cancer, LINC00115 links SETDB1 and PLK3, leading to enhanced SETDB1 methylation of PLK3, which decreases PLK3-mediated phosphorylation of HIF1α, increasing HIF1α stability and promoting chemoresistant breast cancer stem-like cell phenotypes [1]. In glioblastoma, PLK3 promotes the proneural-mesenchymal transition and radioresistance via transcriptional regulation of C5AR1, and its high expression is associated with poor prognosis [3]. In colorectal cancer, a high tumor PLK3-positive rate is related to increased tumor stage and unfavorable survival [6]. In renal ischemia-reperfusion injury, PLK3 is involved in oxidative stress-induced DNA damage and renal tubular epithelial cell apoptosis, and its inhibition attenuates this apoptosis by blocking the ATM/P53-mediated DNA damage response [7]. In swine influenza virus infection, PLK3 interacts with the viral nucleoprotein, promoting viral replication [5].

In summary, Plk3 has diverse functions in cell cycle regulation, apoptosis, and stress response. Studies using different models have revealed its significance in various disease conditions such as cancer and viral infections, highlighting its potential as a therapeutic target in these areas.

References:

1. Luo, Fei, Zhang, Mingda, Sun, Bowen, Li, Yanxin, Feng, Haizhong. 2024. LINC00115 promotes chemoresistant breast cancer stem-like cell stemness and metastasis through SETDB1/PLK3/HIF1α signaling. In Molecular cancer, 23, 60. doi:10.1186/s12943-024-01975-3. https://pubmed.ncbi.nlm.nih.gov/38520019/

2. Myer, David L, Bahassi, El Mustapha, Stambrook, Peter J. . The Plk3-Cdc25 circuit. In Oncogene, 24, 299-305. doi:. https://pubmed.ncbi.nlm.nih.gov/15640846/

3. Yu, Shuo, Lv, Lin, Li, Yang, Liu, Tingting, Hu, Tinghua. 2023. PLK3 promotes the proneural-mesenchymal transition in glioblastoma via transcriptional regulation of C5AR1. In Molecular biology reports, 50, 8249-8258. doi:10.1007/s11033-023-08716-7. https://pubmed.ncbi.nlm.nih.gov/37568042/

4. Helmke, C, Becker, S, Strebhardt, K. 2015. The role of Plk3 in oncogenesis. In Oncogene, 35, 135-47. doi:10.1038/onc.2015.105. https://pubmed.ncbi.nlm.nih.gov/25915845/

5. Ren, Caiyue, Chen, Tong, Zhang, Shishuo, Suolang, Sizhu, Zhou, Hongbo. 2023. PLK3 facilitates replication of swine influenza virus by phosphorylating viral NP protein. In Emerging microbes & infections, 12, 2275606. doi:10.1080/22221751.2023.2275606. https://pubmed.ncbi.nlm.nih.gov/37874309/

6. Zeng, Hai, Wang, Qian, Xiang, Ying, Li, Shuang, Zhang, Weijia. 2024. PLK3 is linked with higher tumor stage and unfavorable prognosis in patients with colorectal cancer. In Biomarkers in medicine, 18, 221-230. doi:10.2217/bmm-2023-0591. https://pubmed.ncbi.nlm.nih.gov/38629862/

7. Deng, Weiming, Wei, Xiangling, Xie, Zhenwei, Li, Heng, Na, Ning. 2022. Inhibition of PLK3 Attenuates Tubular Epithelial Cell Apoptosis after Renal Ischemia-Reperfusion Injury by Blocking the ATM/P53-Mediated DNA Damage Response. In Oxidative medicine and cellular longevity, 2022, 4201287. doi:10.1155/2022/4201287. https://pubmed.ncbi.nlm.nih.gov/35783188/