DYRK3, short for dual-specificity tyrosine-phosphorylation-regulated kinase 3, is a key kinase involved in multiple biological processes. It belongs to the DYRK family and plays essential roles in processes such as secretory trafficking, where it maintains the liquid-like state of ER exit sites (ERESs), thus enabling directional membrane traffic in eukaryotic cells [1]. It is also associated with pathways related to cell growth, differentiation, and stress response. Genetic models, like knockout mice, have been valuable in studying its functions.

DYRK3 knockout (KO) mouse experiments show that in anemia, DYRK3 -/- mice exhibit enhanced erythropoiesis, indicating that DYRK3 attenuates red cell production selectively during anemia [4]. In glioblastoma, knockdown of DYRK3 inhibits mitochondrial fission, leading to increased oxidative phosphorylation and reduced glycolysis, and impairs cell migration and invasion, suggesting its role in promoting glioblastoma malignancy [3]. In oral squamous cell carcinoma (OSCC), inhibition of DYRK3 can combat radiotherapy resistance, highlighting the role of the DYRK3/PAICS axis in OSCC radiotherapy resistance pathways [2].

In conclusion, DYRK3 is crucial for regulating multiple biological processes. KO mouse models have revealed its significant roles in diseases such as anemia, glioblastoma, and OSCC. Understanding DYRK3 functions provides insights into disease mechanisms and may offer potential therapeutic targets for these diseases.

References:

1. Gallo, Raffaella, Rai, Arpan Kumar, McIntyre, Alexa B R, Meyer, Katrina, Pelkmans, Lucas. 2023. DYRK3 enables secretory trafficking by maintaining the liquid-like state of ER exit sites. In Developmental cell, 58, 1880-1897.e11. doi:10.1016/j.devcel.2023.08.005. https://pubmed.ncbi.nlm.nih.gov/37643612/

2. Huang, Chin-Sheng, Hsieh, Ming-Shou, Yadav, Vijesh Kumar, Yeh, Chi-Tai, Huang, Mao-Suan. 2023. PAICS/DYRK3 Multienzyme Interactions as Coregulators of Purinosome Formation and Metabolism on Radioresistance in Oral Squamous Cell Carcinoma. In International journal of molecular sciences, 24, . doi:10.3390/ijms242417346. https://pubmed.ncbi.nlm.nih.gov/38139175/

3. Kim, Kyeongmin, Lee, Sungmin, Kang, Hyunkoo, Youn, HyeSook, Youn, BuHyun. 2021. Dual Specificity Kinase DYRK3 Promotes Aggressiveness of Glioblastoma by Altering Mitochondrial Morphology and Function. In International journal of molecular sciences, 22, . doi:10.3390/ijms22062982. https://pubmed.ncbi.nlm.nih.gov/33804169/

4. Bogacheva, Olga, Bogachev, Oleg, Menon, Madhu, Erickson-Miller, Connie L, Wojchowski, Don M. 2008. DYRK3 dual-specificity kinase attenuates erythropoiesis during anemia. In The Journal of biological chemistry, 283, 36665-75. doi:10.1074/jbc.M807844200. https://pubmed.ncbi.nlm.nih.gov/18854306/