Evolutionary functional analysis and molecular regulation of the ZEB transcription factors

Cell Mol Life Sci. 2012 Aug;69(15):2527-41. doi: 10.1007/s00018-012-0935-3. Epub 2012 Feb 21.


ZEB1 and ZEB2, which are members of the ZEB family of transcription factors, play a pivotal role in the development of the vertebrate embryo. However, recent evidence shows that both proteins can also drive the process of epithelial-mesenchymal transition during malignant cancer progression. The understanding of how both ZEBs act as transcription factors opens up new possibilities for future treatment of advanced carcinomas. This review gives insight into the molecular mechanisms that form the basis of the multitude of cellular processes controlled by both ZEB factors. By using an evolutionary approach, we analyzed how the specific organization of the different domains and regulatory sites in ZEB1 and ZEB2 came into existence. On the basis of this analysis, a detailed overview is provided of the different cofactors and post-translational mechanisms that are associated with ZEB protein functionality.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 5' Untranslated Regions
  • Alcohol Oxidoreductases / chemistry
  • Alcohol Oxidoreductases / metabolism
  • Animals
  • Carcinoma / etiology
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • Epithelial-Mesenchymal Transition / genetics
  • Epithelial-Mesenchymal Transition / physiology
  • Evolution, Molecular
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism*
  • Humans
  • Models, Biological
  • Multiprotein Complexes
  • Neural Crest / embryology
  • Neural Crest / metabolism
  • Phylogeny
  • Promoter Regions, Genetic
  • Signal Transduction
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Transforming Growth Factor beta / metabolism
  • Zinc Fingers / genetics


  • 5' Untranslated Regions
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Multiprotein Complexes
  • Transcription Factors
  • Transforming Growth Factor beta
  • Alcohol Oxidoreductases
  • C-terminal binding protein