P63 Regulates Human Keratinocyte Proliferation Via MYC-Regulated Gene Network and Differentiation Commitment Through Cell Adhesion-Related Gene Network

The study investigated the roles of p63 and MYC in human keratinocyte proliferation and differentiation, revealing that p63 was crucial for both processes. p63 regulated MYC expression via the Wnt/β-catenin and Notch signaling pathways, affecting proliferation, and controlled a gene network related to cell adhesion and migration, vital for differentiation. Knockdown of p63 reduced MYC levels and inhibited differentiation, as shown by decreased expression of early differentiation markers K1 and K10. Both p63 and MYC knockdown led to cell cycle arrest in the G0/G1 phase, with increased expression of cell cycle inhibitors p15 and p21. The study highlighted the distinct roles of p63 and MYC, with p63 being essential for maintaining keratinocyte growth and differentiation.