Transcriptional repression of miR-34 family contributes to p63-mediated cell cycle progression in epidermal cells

Dario Antonini, Monia T. Russo, Laura De Rosa, Marisa Gorrese, Luigi Del Vecchio, Caterina Missero

Research output: Contribution to journalArticlepeer-review

Abstract

p63, a p53 family member, is highly expressed in the basal proliferative compartment of the epidermis and its expression has been correlated with the growth ability and regenerative capacity of keratinocytes. In this study we report a mechanism through which p63 maintains cell cycle progression by directly repressing miR-34a and miR-34c. In the absence of p63, increased levels of miR-34a and miR-34c were observed in primary keratinocytes and in embryonic skin, with concomitant G1-phase arrest and inhibition of the cell cycle regulators cyclin D1 and cyclin-dependent kinase 4 (Cdk4). p63 directly bound to p53-consensus sites in both miR-34a and miR-34c regulatory regions and inhibited their activity. Concomitant downregulation of miR-34a and miR-34c substantially restored cell cycle progression and expression of cyclin D1 and Cdk4. Our data indicate that specific miR-34 family members have a significant role downstream of p63 in controlling epidermal cell proliferation.

Original languageEnglish
Pages (from-to)1249-1257
Number of pages9
JournalJournal of Investigative Dermatology
Volume130
Issue number5
DOIs
Publication statusPublished - May 2010

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Transcriptional repression of miR-34 family contributes to p63-mediated cell cycle progression in epidermal cells'. Together they form a unique fingerprint.

Cite this