C-terminal binding protein 1 (CtBP1) (CtBP1)

C-terminal binding protein 1 (CtBP1) is a highly conserved transcriptional corepressor that regulates gene expression by recruiting chromatin-modifying enzymes to DNA-binding transcription factors (UniProt Q13363). It primarily interacts with partners through a conserved PXDLS (Pro-X-Asp-Leu-Ser) motif, which binds to a specific hydrophobic cleft on the CtBP1 surface (PMID: 25605895). In many cancers, CtBP1 is overexpressed and promotes the epithelial-mesenchymal transition (EMT), cell survival, and metastasis by repressing tumor suppressors like E-cadherin (PMID: 21685939). The CtBP1-transcription factor interface has emerged as a significant therapeutic target, with small molecules and cyclic peptides being developed to disrupt these protein-protein interactions (PMID: 31431518). Additionally, CtBP1 possesses a D-isomer specific 2-hydroxyacid dehydrogenase domain, where NADH binding induces a conformational change that enhances its oligomerization and corepressor activity (PMID: 12446775). Targeting this interface or the metabolic pocket offers a strategy to reverse oncogenic transcriptional programs and sensitize tumors to chemotherapy (PMID: 28240267).

Other names

C-terminal-binding protein 1CtBPBARSBrefeldin A-ADP ribosylated substrateCtBP1-transcription factor interface

Disruption of the protein-protein interaction (PPI) between CtBP1 and PXDLS-containing transcription factors by binding to the PXDLS-binding cleft or the NADH-binding site, thereby preventing the recruitment of chromatin-modifying complexes.