Biochemical and biophysical research communicationsDec 24, 2019

CtBP2 controls cell changes linked to movement by working with OCT1 in a new protein complex

Updated Feb 27, 2026

Abstract

C-terminal binding protein 2 (CtBP2) may orchestrate the epithelial to mesenchymal transition (EMT) program through a novel interaction with the transcription factor OCT1.

CtBP2 is identified as a critical transcriptional co-repressor involved in regulating the EMT program.
A direct interaction between CtBP2 and the transcription factor OCT1 is observed.
OCT1 appears to accelerate the EMT program, which is reduced by mutations affecting its interaction with CtBP2.
Transforming growth factor-β (TGF-β) promotes the formation of the CtBP2/OCT1 complex, suggesting a regulatory mechanism.
These findings illustrate the potential for therapeutic targeting of the CtBP2/OCT1 interaction in various diseases.

Simplified

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.

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