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Significance The Runt-related transcription factors (RUNX) are critical regulators of development. Mutation or dysregulation ofRUNX genes have been associated with diverse cancer types. Phosphorylation of the strictly conserved threonine 173 (T173) residue within the Runt domain of RUNX3 disrupts DNA binding activity, which facilitates the recruitment of RUNX proteins to mitotic structures. Moreover,RUNX3 deficiency is associated with delayed mitotic entry. The tight conservation of T173 and its flanking residues from unicellular organism to human, and the fact that mitosis is indispensable to all metazoans, strongly indicate that T173 phosphorylation is fundamental to the role of RUNX in these divergent organisms. Cancer-associated mutation T173I further corroborates the critical role of RUNX phosphorylation in mitosis.

Aurora kinase-induced phosphorylation excludes transcription factor RUNX from the chromatin to facilitate proper mitotic progression