CTBP

CtBP, or C-terminal binding protein, refers to a family of transcriptional corepressors in animals, represented in humans by two paralogs: CTBP1 and CTBP2. CtBP proteins function as chromatin-associated corepressors that help repress target genes in cooperation with sequence-specific transcription factors. They are conserved from flies to humans and play roles in development, cellular differentiation, and metabolism, as well as in cancer progression through regulation of epithelial-mem

brain EMT processes and gene expression programs.

CtBP proteins are dimeric, NAD+-binding enzymes with a catalytic-like N-terminal domain and a C-terminal dimerization region. They can bind NAD+, and this cofactor binding is linked to their biochemical activity and regulatory state. CtBP interacts with transcription factors through conserved binding motifs, notably PLDLS and related PXDLS-like sequences, allowing recruitment to promoters and enhancers. Once localized to chromatin, CtBP forms repressive complexes by engaging chromatin-modifying enzymes, such as histone deacetylases and other epigenetic factors, to silence transcription.

Biological roles of CtBP include regulation of development and cell fate decisions, control of genes involved in cell adhesion and metabolism, and modulation of Wnt signaling in some contexts. In cancer, CtBP contributes to tumor progression and metastasis by promoting epithelial-mesenchymal transition and repressing tumor suppressor genes. Given its central role as a transcriptional corepressor, CtBP is explored as a potential target for therapeutic intervention, with approaches aiming to disrupt NAD+-binding or protein–protein interactions that recruit CtBP to target genes.

CtBP2 and CtBP1 differ in isoform expression and subcellular localization, with multiple splice variants giving rise to nuclear and potentially cytoplasmic forms that tailor their transcriptional repression activities to cellular context.