Cdk5r1, also known as cyclin-dependent kinase 5 regulatory subunit 1, encodes for p35, the main activator of Cyclin-dependent kinase 5 (CDK5). The active p35/CDK5 complex is involved in numerous aspects of brain development and function [6]. It has been associated with pathways like notch signaling [1]. Cdk5r1 is of great biological importance as it participates in processes such as central nervous system development and neuronal migration [2]. Genetic models are valuable for studying its function.

In hepatocellular carcinoma (HCC), high Cdk5r1 expression is significantly associated with tumor status, new tumor event, clinical stage, and topography, and predicts worse overall survival, disease-specific survival, disease-free interval, and progression-free interval [1]. In peripheral nerve injury, overexpression of Cdk5r1 promotes Schwann cell proliferation, migration, and inhibits apoptosis, and it also promotes nerve injury recovery in rats through the CDK5 mediated BDNF/TrkB pathway [2]. In β -cells, Cdk5r1 overexpression induces primary β -cell proliferation while maintaining glucose-stimulated insulin secretion and confers protection against certain apoptosis-inducing agents [3]. In Ewing's sarcoma cells, miR-152 suppresses cell proliferation by targeting Cdk5r1 [4]. In colorectal and breast malignancies, elevated Cdk5r1 expression is associated with poor prognosis, proliferation, and drug resistance [5]. In Alzheimer's disease, its expression is regulated by long non-coding RNAs, and it has been linked to disease onset and progression [6].

In conclusion, Cdk5r1 is crucial for normal development and function, especially in the nervous system. Its dysregulation is associated with various diseases, including cancers and Alzheimer's disease. Model-based research, though not specifically highlighting KO/CKO mouse models in the provided references, has shown its role in disease-related biological processes, providing insights into potential therapeutic targets.

References:

1. Zeng, Zhili, Cao, Zebiao, Zhang, Enxin, Huang, Haifu, Tang, Ying. . Elevated CDK5R1 predicts worse prognosis in hepatocellular carcinoma based on TCGA data. In Bioscience reports, 41, . doi:10.1042/BSR20203594. https://pubmed.ncbi.nlm.nih.gov/33346796/

2. Xia, Lei, Li, Peng, Bi, Wenchao, Yang, Ruize, Zhang, Yuelin. 2023. CDK5R1 promotes Schwann cell proliferation, migration, and production of neurotrophic factors via CDK5/BDNF/TrkB after sciatic nerve injury. In Neuroscience letters, 817, 137514. doi:10.1016/j.neulet.2023.137514. https://pubmed.ncbi.nlm.nih.gov/37848102/

3. Draney, Carrie, Hobson, Amanda E, Grover, Samuel G, Jack, Benjamin O, Tessem, Jeffery S. 2015. Cdk5r1 Overexpression Induces Primary β-Cell Proliferation. In Journal of diabetes research, 2016, 6375804. doi:10.1155/2016/6375804. https://pubmed.ncbi.nlm.nih.gov/26788519/

4. Kawano, Masanori, Tanaka, Kazuhiro, Itonaga, Ichiro, Kubota, Yuta, Tsumura, Hiroshi. 2023. Tumor-suppressive microRNA-152 inhibits the proliferation of Ewing's sarcoma cells by targeting CDK5R1. In Scientific reports, 13, 18546. doi:10.1038/s41598-023-45833-6. https://pubmed.ncbi.nlm.nih.gov/37899376/

5. Dastjerdi, Shaghayegh, Haghparast, Amin, Amroabadi, Jalal Mosayebi, Mahdevar, Mohammad, Ghaedi, Kamran. 2022. Elevated CDK5R1 expression associated with poor prognosis, proliferation, and drug resistance in colorectal and breast malignancies: CDK5R1 as an oncogene in cancers. In Chemico-biological interactions, 368, 110190. doi:10.1016/j.cbi.2022.110190. https://pubmed.ncbi.nlm.nih.gov/36162454/

6. Spreafico, Marco, Grillo, Barbara, Rusconi, Francesco, Battaglioli, Elena, Venturin, Marco. 2018. Multiple Layers of CDK5R1 Regulation in Alzheimer's Disease Implicate Long Non-Coding RNAs. In International journal of molecular sciences, 19, . doi:10.3390/ijms19072022. https://pubmed.ncbi.nlm.nih.gov/29997370/