Transactivation of the cyclin A promoter by bovine papillomavirus type 4 E5 protein

Bovine papillomavirus type 4 (BPV-4) E5 (formerly E8) is a 42-residue hydrophobic, membrane-localised protein that can transform NIH-3T3 cells by a poorly defined mechanism. In E5-expressing cells, the observed up-regulation of cyclin A is underpinned by transactivation of the cyclin A promoter. Here we show that E5 transactivates the minimal cell cycle-regulated cyclin A promoter in cells both stably and acutely expressing the viral protein. There are no detectable differences between control and E5 cells in protein complexes binding the E2F-like cell cycle-dependent element (CDE)/cell cycle-regulated element (CCRE) of the cyclin A promoter and E5 does not transactivate E2F reporter plasmids in an E2F-dependent manner in vivo. CCAAT box integrity and functional NF-Y complexes are required for E5-mediated transactivation and a Mr approximately 110 K CCAAT-box binding factor (p110 CBF) associates with NF-YA only in E5 cells. This suggests that E5 sets the extent of cyclin A promoter activation by a mechanism similar to other, structurally unrelated, DNA tumour virus oncoproteins but distinct from the action of serum factors and so is inconsistent with E5 acting through constitutive activation of tyrosine kinase growth factor receptors.