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DYRK1A and the Cell Cycle
The ability to halt the cell cycle is critical for cells to maintain tissue and organ size, to suppress tumors and abnormal growth, and exists as a helpful mechanism to pause the cell cycle for DNA repair. DYRK1A is (dual specificity tyrosine-(Y)-phosphorylation regulated kinase 1A) a human gene found on the long (q) arm of chromosome 21, which is known to be involved with nervous system development, cell growth and division, and neuronal differentiation. In glioblastoma cells grown in vitro (T98G cell line), there are three copies of DYRK1A, which have dosage- dependent effects on the cell, including association with cognitive delays in Down Syndrome (Trisomy 21), and relevance to cancer (loss of DYRK1A leads to oncogenic transformation of fallopian tube epithelial cells by Ras and p53). In terms of DYRK1A’s role in the cell cycle, it is known as a putative tumor suppressor, mainly through its critical role in phosphorylating a Serine 28 residue on protein LIN52, leading to the formation of the DREAM complex. DREAM promotes exit from the cell cycle and cell quiescence (arrest in G0 phase). Surprisingly, DYRK1A-KO (knockout) cells actually slowed down cell proliferation, which is an unexpected result when knocking out a tumor suppressor. Through several experiments, involving cell cycle flow cytometry, western blotting for protein cell cycle markers, and EdU staining to determine whether these cells were actively undergoing DNA synthesis, we were able to determine that DYRK1A-KO T98G cells were entering the cell cycle and undergoing DNA synthesis more slowly that control cells.https://scholarscompass.vcu.edu/gradposters/1068/thumbnail.jp