Contribution of CDP/Cux, a transcription factor, to cell cycle progression.

Abstract

CCAAT-displacement protein/Cut homeobox (CDP/Cux) was initially identified as a transcriptional repressor. However, a number of studies have now suggested that CDP/Cux is a transcriptional activator as well. Stable DNA binding activity of CDP/Cux is up-regulated at the G(1)/S transition by two mechanisms, dephosphorylation by the Cdc25A phosphatase and proteolytic processing to generate a 110 kDa amino-truncated isoform, CDP/Cux p110. The generation of CDP/Cux p110 stimulates the expression of reporter plasmid containing the promoter sequences of some S phase-specific-genes such as DNA polymerase a gene, dihydrofolate reductase gene, carbamoyl-phosphate synthase/aspartate carbamoyl-transferase/dihydroorotase gene, and cyclin A gene. However, DNA binding activity of CDP/Cux is down-regulated at G(2) phase through a binding of cyclin A-cyclin-dependent kinases1 (Cdk1) to CDP/Cux. Furthermore, another CDP/Cux isoform, CDP/Cux p75, has been found to be associated with breast tumors indicating this isoform is involved in the abnormal proliferation of tumor cells. The differences in DNA binding of CDP/Cux isoforms in S and G(2) phases suggest important roles of CDP/Cux in cell cycle progression. In this review, we discuss the functions of CDP/Cux with a focus on its roles in cell cycle regulation and its possible potency leading to the cell cycle reentry of neurons.