Control of melanocyte differentiation by a MITF-PDE4D3 homeostatic circuit

Mehdi Khaled, Carmit Levy, David E. Fisher

Research output: Contribution to journalArticlepeer-review

Abstract

Cyclic AMP (cAMP) is a ubiquitous second messenger that regulates a variety of biological processes. The magnitude and duration of cAMP expression are regulated by both production and hydrolysis. Melanocyte-stimulating hormone (MSH) plays a crucial role in pigment cell differentiation via cAMP-regulated expression of the master transcription factor MITF. We report the identification of phosphodiesterase 4D3 as a direct target of the MSH/cAMP/MITF pathway. This creates a negative feedback loop that induces refractoriness to chronic stimulation of the cAMP pathway in melanocytes. This homeostatic pathway highlights a potent mechanism controlling melanocyte differentiation that may be amenable to pharmacologic manipulation for skin cancer prevention.

Original languageEnglish
Pages (from-to)2276-2281
Number of pages6
JournalGenes and Development
Volume24
Issue number20
DOIs
StatePublished - 15 Oct 2010
Externally publishedYes

Keywords

  • MITF
  • PDE4D
  • Pigmentation
  • Skin
  • cAMP

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