Transcriptional co-repressor CtBP2 orchestrates epithelial-mesenchymal transition through a novel transcriptional holocomplex with OCT1

Biochem Biophys Res Commun. 2020 Mar 5;523(2):354-360. doi: 10.1016/j.bbrc.2019.12.070. Epub 2019 Dec 19.


The epithelial to mesenchymal transition (EMT) is a cell intrinsic program controlling cellular morphological and phenotypic remodeling in a wide range of biological processes. Despite the accumulating evidence, the transcriptional networks regulating EMT still remain to be elucidated. In this study, we demonstrate that C-terminal binding protein 2 (CtBP2), a critical transcriptional co-repressor harboring pyridine nucleotide sensing capability, orchestrates the EMT program at least in part through a novel transcriptional interaction with an octamer transcription factor, OCT1 (POU2F1, POU class 2 homeobox 1). We identified novel interactions of CtBP2 with several octamer transcription factors, and CtBP2 exhibits a direct interaction with OCT1 in particular. OCT1 accelerates the EMT program as reported, which is diminished by the mutation of the CtBP-binding motif in OCT1, suggesting OCT1 represses epithelial gene expression through recruiting the co-repressor CtBP2. In accordance with these findings, a canonical EMT activator transforming growth factor-β (TGF-β) promotes the formation of the CtBP2/OCT1 complex. Our observations illustrate the role of CtBP2 to orchestrate the EMT program through the interaction with OCT1 and highlight the potential of therapeutic exploitation of this new transcriptional system for a wide range of diseases.

Keywords: CtBP2; EMT; OCT1; Transcriptional complex.

MeSH terms

  • Alcohol Oxidoreductases / chemistry
  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Co-Repressor Proteins / chemistry
  • Co-Repressor Proteins / genetics
  • Co-Repressor Proteins / metabolism*
  • Conserved Sequence
  • Epithelial-Mesenchymal Transition / genetics
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Gene Regulatory Networks
  • Humans
  • MCF-7 Cells
  • Mice
  • Mutation
  • Octamer Transcription Factor-1 / chemistry
  • Octamer Transcription Factor-1 / genetics
  • Octamer Transcription Factor-1 / metabolism*
  • Protein Interaction Domains and Motifs
  • Rats
  • Transforming Growth Factor beta / metabolism


  • Co-Repressor Proteins
  • Octamer Transcription Factor-1
  • POU2F1 protein, human
  • Transforming Growth Factor beta
  • Alcohol Oxidoreductases
  • CTBP2 protein, human