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Development 2006 Sep 01;13317:3359-70. doi: 10.1242/dev.02504.
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Slug stability is dynamically regulated during neural crest development by the F-box protein Ppa.

Vernon AE , LaBonne C .

The neural crest is a population of stem-cell-like precursors found only in vertebrates. Slug, a member of the Snail family of zincfinger 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 developmental and pathological epithelial to mesenchymal transitions.

PubMed ID: 16887825
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: actl6a ctnnb1 fbxl14 foxd3 gal.2 grap2 id3 mapk14 myc smad1 snai1 snai2 sox10 sox3 sox9 twist1 zic1
Morpholinos: fbxl14 MO1

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