Molecular and Cellular Function of p63 in Skin Development and Genetic Diseases

J Invest Dermatol. 2025 Apr;145(4):766-779. doi: 10.1016/j.jid.2024.08.011. Epub 2024 Sep 26.

Abstract

The transcription factor p63 is a master regulator of multiple ectodermal derivatives. During epidermal commitment, p63 interacts with several chromatin remodeling complexes to transactivate epidermal-specific genes and repress transcription of simple epithelial and nonepithelial genes. In the postnatal epidermis, p63 is required to control the proliferative potential of progenitor cells, maintain epidermal integrity, and contribute to epidermal differentiation. Autosomal dominant sequence variant in p63 cause a spectrum of syndromic disorders that affect several tissues, including or derived from stratified epithelia. In this review, we describe the recent studies that have provided novel insights into disease pathogenesis and potential therapeutic targets.

Keywords: Ectodermal dysplasia; Embryonic development; Epidermis; Genetic disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Epidermis
  • Humans
  • Skin Diseases, Genetic* / genetics
  • Skin* / embryology
  • Skin* / growth & development
  • Trans-Activators* / genetics
  • Transcription Factors* / genetics
  • Transcription Factors* / physiology
  • Tumor Suppressor Proteins* / genetics
  • Tumor Suppressor Proteins* / physiology

Substances

  • Transcription Factors
  • Tumor Suppressor Proteins
  • TP63 protein, human
  • Trans-Activators