CDK9 Kinase Activation in Association with AFF1-SEC Initiates Epidermal Progenitor Differentiation

The study investigates the role of CDK9 kinase activity in epidermal progenitor differentiation, highlighting its association with the Super Elongation Complex (SEC). In progenitor-state keratinocytes, CDK9 is inactive and maintained by HEXIM1 and AFF1. Disruption of SEC or activation of Protein kinase C (PKC) signaling activates CDK9, leading to rapid upregulation of genes with "paused" Pol II, including ATF3. Overexpression of ATF3 triggers other differentiation factors and reduces clonogenicity in keratinocytes. The findings suggest that CDK9 activation, influenced by AFF1 and HEXIM1, is crucial for initiating epidermal progenitor differentiation in response to cellular signals.