The retinoblastoma gene and its product are targeted by ICBP90: a key mechanism in the G1/S transition during the cell cycle.

The retinoblastoma protein (pRB) is encoded by the RB1 gene whose promoter contains several putative binding sites for ICBP90 (Inverted CCAAT box Binding Protein of 90 kDa), a transcriptional regulator of the topoisomerase IIalpha gene. ICBP90 has two consensus binding sites for pRB in its primary sequence. Here, we show that pRB and ICBP90 co-immunoprecipitate in cell extracts of proliferating human lung fibroblasts and of proliferating or confluent Jurkat cells.

ICBP90 expression is downregulated in apoptosis-induced Jurkat cells.

Inhibition of apoptosis, resulting from an increase in anti-apoptotic protein, plays a fundamental role in carcinogenesis. Because ICBP90 gene expression is deregulated in cancer cells, we studied its expression in Jurkat cells under apoptotic conditions to see whether ICBP90 is involved in the regulation of apoptosis. We found that ICBP90 expression and the percentage of living cells were dose-dependently decreased in PHA and ionophore A23187-stimulated Jurkat cells, but not in THP-1 cells.

Overexpression of ICBP90, a novel CCAAT-binding protein, overcomes cell contact inhibition by forcing topoisomerase II alpha expression.

We have recently identified ICBP90 as being a protein able to bind in vitro a CCAAT box of the topoisomerase II alpha gene promoter. The aim of the present work was to check whether ICBP90 is able to regulate in vivo topoisomerase II alpha expression in human lung fibroblasts under various proliferating conditions. Transient transfection experiments performed on moderately growing human lung fibroblasts (50% of confluence) showed that overexpression of ICBP90 is associated with an elevation of topoisomerase II alpha expression and an increase of the cell proliferation rate.

Transcriptional regulation of the human topoisomerase IIalpha gene.

In this paper, we review the current literature about the transcriptional regulation of the topoisomerase IIalpha gene. The interpretation of the results obtained from many different studies is complicated by clear species-specific differences in the spatial organisation of DNA regulatory elements in the topoisomerase IIalpha gene promoter. However, the present review aims to emphasise the critical role played by some DNA sequences in the promoter of the topoisomerase IIalpha gene with special attention to the role of CCAAT sequences that are positioned in the inverted orientation.