The transcriptional co-repressor C-terminal Binding Protein (CtBP) associates with centrosomes during mitosis

Abstract

CtBP is a corepressor of transcription that acts by inhibiting coactivators and recruiting to promoter control elements (via interactions with DNA-binding transcription factors) a complex of proteins that modify histones, repress transcription and silence gene expression. There are two highly homologous genes, CtBP1 and CtBP2 that encode CtBP. In addition, a CtBP1-related protein has been described that has 11 fewer amino acids at its N-terminus than CtBP1. This variant of CtBP1 - known as CtBP3 or BARS [Brefeldin A (BFA) ribosylated substrate] - plays a critical role in the fragmentation of the Golgi complex at the onset of mitosis. Although there are some reports of CtBP with a cytoplasmic distribution after transfection, it is unclear how in normal cells a nuclear corepressor regulates the behavior of the Golgi complex at the onset of mitosis. Using polyclonal rabbit antibodies that were raised against a human CtBP1-GST fusion-protein, here we show by immunofluorescence laser-scanning confocal microscopy that in mitotic cells a species of CtBP becomes associated with the centrosomes at the onset of prophase and then throughout mitosis. The association can be seen in both cycling mitotic cells and nocodazole-arrested cells. The interaction was confirmed by coimmunoprecipitation and centrosome isolation. Since centrosomes are considered to be the organizing centre for Golgi morphogenesis, the interaction demonstrated here may explain how a nuclear corepressor of transcription can exert a regulatory effect on the Golgi complex at a specific stage of the cell cycle. ©2006 Landes Bioscience.