DYRK3 Protein, Human (Active, sf9, His-GST)

DYRK3, a dual-specificity protein kinase, plays a pivotal role in orchestrating the disassembly of various membraneless organelles, including stress granules, nuclear speckles, and pericentriolar material, during mitosis. Operating as a central dissolvase during the G2-to-M transition, DYRK3 achieves this by phosphorylating multiple serine and threonine residues in unstructured domains of target proteins, such as SRRM1 and PCM1. Notably, DYRK3's dissolving activity is selective, sparing membraneless organelles like P-bodies and the nucleolus. This orchestrated disassembly is crucial for releasing mitotic regulators, including ZNF207, from liquid-unmixed organelles, preventing their sequestration and maintaining dissolution during mitosis. Additionally, DYRK3 regulates mTORC1 by mediating stress granule dissolution and facilitating mTORC1 relocation to the cytosol, a process essential for full reactivation of mTORC1 signaling. Beyond its role in organelle dynamics, DYRK3 emerges as a negative regulator of EPO-dependent erythropoiesis, potentially imposing an upper limit on red cell production during stress erythropoiesis. Furthermore, DYRK3 exhibits a pro-survival function, inhibiting cell death induced by cytokine withdrawal in hematopoietic progenitor cells and promoting cell survival under genotoxic stress through the phosphorylation of SIRT1, consequently inhibiting p53/TP53 activity and apoptosis.