C-terminal binding protein-mediated transcriptional repression is regulated by X-linked inhibitor of apoptosis protein

► Diap1 bound to dCtBP, a transcriptional co-repressor in S2 cells. CtBP1 also interacted with XIAP in human cells. ► CtBPs were ubiquitinated by IAPs and targeted for proteasome-mediated degradation. ► The expression of CtBP1 target genes was regulated by XIAP expression. ► XIAP may play a role in regulating CtBP1-mediated transcriptional repression. Inhibitors of Apoptosis Proteins (IAPs) are known as the key negative regulators of apoptosis. To explore new functions of IAPs, we sought to identify proteins that interact with Diap1 in insect S2 cells. We found that Diap1 bound to Drosophila C-terminal binding protein (dCtBP), which is a transcriptional co-repressor. CtBP1 also interacted with X-linked inhibitor of apoptosis protein (XIAP) in human cells. CtBPs were ubiquitinated by IAPs and targeted for proteasome-mediated degradation. Finally, the expression of CtBP1 target genes was regulated by XIAP expression. This is the first report to demonstrate that XIAP specifically regulates CtBP1, suggesting that XIAP may play a role in regulating CtBP1-mediated transcriptional repression by regulating the level of CtBP1.