Slug stability is dynamically regulated during neural crest development by the F-box protein Ppa

Ann E. Vernon, Carole LaBonne*

*Corresponding author for this work

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

The neural crest is a population of stem-cell-like precursors found only in vertebrates. Slug, a member of the Snail family of zinc-finger transcriptional repressors, is a critical regulator of neural crest development and has also been implicated in the acquisition of invasive behavior during tumor progression. Despite its central role in these two important processes, little is known about the mechanisms that control the expression and/or activity of Slug. We demonstrate that Slug is a labile protein whose stability is positively reinforced through activation of the neural crest regulatory program. We identify Partner of paired (Ppa) as the F-box component of a modular E3 ligase, and show that it is expressed in neural crest-forming regions, and that it binds to and promotes ubiquitin-mediated proteasomal degradation of Slug. Misexpression of Ppa inhibits the formation of neural crest precursors, and Slug mutants in which Ppa binding has been abrogated rescue this inhibition. These results provide novel insight into the regulation of Slug, a protein that plays a central role in neural crest precursor formation, as well as in development and pathological epithelial to mesenchymal transitions.

Original languageEnglish (US)
Pages (from-to)3359-3370
Number of pages12
JournalDevelopment
Volume133
Issue number17
DOIs
StatePublished - Sep 1 2006

Keywords

  • Neural crest
  • Ppa
  • Slug
  • Snail
  • Ubiquitin
  • Xenopus

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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