C-terminal-binding protein 1 (CtBP1)

C-terminal-binding protein 1 (CtBP1) is an evolutionarily conserved transcriptional corepressor and metabolic sensor encoded by the CTBP1 gene. CtBP1 is recruited to gene promoters by sequence-specific transcription factors and mediates transcriptional repression by interacting with chromatin-modifying complexes, including histone deacetylases and polycomb group proteins[1][2][5]. Its corepressor function is regulated by its binding to NADH, enabling CtBP1 to sense cellular metabolic states and coordinate gene expression with energy status[1][7]. CtBP1 plays critical roles in development, cell differentiation, cell proliferation, regulation of mitochondrial function, and membrane trafficking (particularly as BARS)[1][2][5][7]. Overexpression or hyperactivity of CtBP1 is associated with cancer, as it represses tumor suppressor genes, promotes epithelial-mesenchymal transition, and enhances tumor cell migration and metastasis[3][4]. Several preclinical small molecule inhibitors have been developed targeting CtBP1, notably in cancer research[3]. Loss of function mutations are linked to developmental disorders, while broad inhibition poses significant safety challenges due to its central regulatory roles.

Other names

CtBP1CTBPBARSbrefeldin A-ribosylated substrateHADDTSC-terminal binding protein 1

Inhibition of transcriptional corepressor function (restores tumor suppressor expression, blocks oncogenic repression). Inhibition of dehydrogenase enzymatic activity.