TRANSCRIPTIONAL CONTROL OF THE HTF9-A RANBP-1 GENE DURING THE CELL-CYCLE/

The mouse Htf9-a gene encodes a small hydrophilic protein, named Ran-b inding protein 1 (RanBP-1), for its interaction with the Ras-related R an protein; RanBP-1 binds the biologically active form of Ran. Ran has been implicated in a variety of nuclear events including DNA replicat ion, RNA export and protein import, and monitoring completion of DNA s ynthesis before the onset of mitosis; its biological activity is thoug ht to be regulated in S phase. We have investigated whether expression of the Htf9-a/RanBP-1 gene is linked to cell proliferation. Expressio n of the Htf9-a/RanBP-1 transcript appeared to be dependent on the pro liferating state of the cells and peaked in S phase. We have identifie d a promoter region required for Htf9-a cell cycle-dependent expressio n and for responsiveness to cell cycle regulators. An E2F-binding site was identified within the cell cycle-regulated promoter region. Expre ssion of the E1A oncoprotein prevented Htf9-a down-regulation in quies cent cells; in addition, both pRb and its relative p107 inhibited tran scription from the Htf9-a promoter. These results link the control of Htf9a/RanBP-1 expression to the cell cycle progression.