P63 suppresses non-epidermal lineage markers in a bone morphogenetic protein-dependent manner via repression of Smad7

Laura De Rosa, Dario Antonini, Giustina Ferone, Monia T. Russo, Paul B. Yu, Rong Han, Caterina Missero

Research output: Contribution to journalArticle

Abstract

p63, a p53 family member, plays an essential role in epidermal development by regulating its transcriptional program. Here we report a previously uncovered role of p63 in controlling bone morphogenetic protein (BMP) signaling, which is required for maintaining low expression levels of several non-epidermal genes. p63 represses transcription of the inhibitory Smad7 and activates Bmp7, thereby sustaining BMP signaling. In the absence of p63, compromised BMP signaling leads to inappropriate non-epidermal gene expression in postnatal mouse keratinocytes and in embryonic epidermis. Reactivation of BMP signaling by Smad7 knockdown and/or, to a lesser extent, by BMP treatment suppresses expression of non-epidermal genes in the absence of p63. Canonical BMP/Smad signaling is essential for control of non-epidermal genes as use of a specific inhibitor, or simultaneous knockdown of Smad1 and Smad5 counteract suppression of non-epidermal genes. Our data indicate that p63 prevents ectopic expression of non-epidermal genes by a mechanism involving Smad7 repression and, to a lesser extent, Bmp7 induction, with consequent enhancement of BMP/Smad signaling.

Original languageEnglish
Pages (from-to)30574-30582
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number44
DOIs
Publication statusPublished - Oct 30 2009

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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