Stabilization of ATF4 protein is required for the regulation of epithelial-mesenchymal transition of the avian neural crest

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Epithelial-mesenchymal transition (EMT) permits neural crest cells to delaminate from the epithelial ectoderm and to migrate extensively in the embryonic environment. In this study, we have identified ATF4, a basic-leucine-zipper transcription factor, as one of the neural crest EMT regulators. Although ATF4 alone was not sufficient to drive the formation of migratory neural crest cells, ATF4 cooperated with Sox9 to induce neural crest EMT by controlling the expression of cell-cell and cell-extracellular matrix adhesion molecules. This was likely, at least in part, by inducing the expression of Foxd3, which encodes another neural crest transcription factor. We also found that the ATF4 protein level was strictly regulated by proteasomal degradation and p300-mediated stabilization, allowing ATF4 protein to accumulate in the nuclei of neural crest cells undergoing EMT. Thus, our results emphasize the importance of the regulation of protein stability in the neural crest EMT.

Original languageEnglish
Pages (from-to)658-668
Number of pages11
JournalDevelopmental Biology
Volume344
Issue number2
DOIs
Publication statusPublished - 2010 Aug

Keywords

  • ATF4
  • EMT
  • Foxd3
  • Neural crest
  • P300
  • Sox9

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Stabilization of ATF4 protein is required for the regulation of epithelial-mesenchymal transition of the avian neural crest'. Together they form a unique fingerprint.

Cite this