Cdk5r2, also known as p39, is a non-cyclin activator protein of the atypical cyclin-dependent kinase Cdk5. Cdk5, though present in all cells and tissues, is often associated with neurons due to the abundant presence of its activator proteins there. Cdk5, activated by Cdk5r2, is involved in various biological processes such as transcript-selective translation control, glucose-inducible insulin secretion, and cell migration. It also plays a role in important neuronal functions like dendritic morphogenesis [3,5].

In research, Cdk5r2 has been implicated in multiple disease conditions. In human immunodeficiency virus encephalitis (HIVE), it was identified as one of the hub genes potentially serving as new targets for diagnosis and therapy [1]. In non-small cell lung carcinoma (NSCLC), overexpression of Cdk5r2/p39 was associated with impaired cell adhesion and epithelial-to-mesenchymal transition, suggesting its potential as a biomarker for lung cancer grading and staging [2]. In hepatocellular carcinoma (HCC), a risk model including Cdk5r2 showed prognostic value in predicting survival rates among HCC patients [4]. Also, in pancreatic cancer, Cdk5r2 was among the genes potentially preventing lymph node metastasis [6]. In HCC with vascular invasion, CDK5R2 was negatively correlated to natural killer cells [7].

In conclusion, Cdk5r2 is a crucial activator of Cdk5 involved in diverse biological functions. Studies, especially those on disease models like HIVE, NSCLC, HCC, and pancreatic cancer, have revealed its potential significance as a biomarker and therapeutic target. The research on Cdk5r2 contributes to a better understanding of the molecular mechanisms underlying these diseases, offering new perspectives for diagnosis, prognosis, and treatment.

References:

1. Wang, Shitao, Ding, Xiangqian, Li, Zongyou, Zhang, Mengen, Xie, Zhenrong. 2023. Comprehensive analyses identify potential biomarkers for encephalitis in HIV infection. In Scientific reports, 13, 18418. doi:10.1038/s41598-023-45922-6. https://pubmed.ncbi.nlm.nih.gov/37891420/

2. Pérez-Morales, Jaileene, Mejías-Morales, Darielys, Rivera-Rivera, Stephanie, Koomen, John M, Santiago-Cardona, Pedro G. 2018. Hyper-phosphorylation of Rb S249 together with CDK5R2/p39 overexpression are associated with impaired cell adhesion and epithelial-to-mesenchymal transition: Implications as a potential lung cancer grading and staging biomarker. In PloS one, 13, e0207483. doi:10.1371/journal.pone.0207483. https://pubmed.ncbi.nlm.nih.gov/30452490/

3. Arif, Abul. 2012. Extraneuronal activities and regulatory mechanisms of the atypical cyclin-dependent kinase Cdk5. In Biochemical pharmacology, 84, 985-93. doi:10.1016/j.bcp.2012.06.027. https://pubmed.ncbi.nlm.nih.gov/22795893/

4. Wu, Yingmin, Li, Lian, Wang, Long, Li, Haiyang, Chen, Tengxiang. 2024. m1A regulator-mediated methylation modification patterns correlated with autophagy to predict the prognosis of hepatocellular carcinoma. In BMC cancer, 24, 506. doi:10.1186/s12885-024-12235-4. https://pubmed.ncbi.nlm.nih.gov/38649860/

5. Ouyang, Li, Chen, Yu, Wang, Ye, Fu, Wing-Yu, Ip, Nancy Y. 2020. p39-associated Cdk5 activity regulates dendritic morphogenesis. In Scientific reports, 10, 18746. doi:10.1038/s41598-020-75264-6. https://pubmed.ncbi.nlm.nih.gov/33127972/

6. Qin, Cheng, Li, Tianhao, Wang, Yuanyang, Zhao, Yutong, Wang, Weibin. 2022. CHRNB2 represses pancreatic cancer migration and invasion via inhibiting β-catenin pathway. In Cancer cell international, 22, 340. doi:10.1186/s12935-022-02768-8. https://pubmed.ncbi.nlm.nih.gov/36344976/

7. Cai, Shijiao, Du, Renle, Zhang, Yuan, Yuan, Hengjie, Li, Zhengxiang. 2022. Construction and Comprehensive Analysis of ceRNA Networks and Tumor-Infiltrating Immune Cells in Hepatocellular Carcinoma With Vascular Invasion. In Frontiers in bioinformatics, 2, 836981. doi:10.3389/fbinf.2022.836981. https://pubmed.ncbi.nlm.nih.gov/36304284/