CELL-CYCLE REGULATION OF NUCLEAR FACTOR P92 DNA-BINDING ACTIVITY BY NOVEL PHASE-SPECIFIC INHIBITORS

The nuclear factor p92, originally discovered by its interaction with the human papillomavirus type 18 enhancer, is a cellular protein whose activity is restricted to S phase in human primary fibroblasts, The h uman papillomavirus type 18 p92 binding sequence confers enhancer acti vity on a heterologous promoter, suggesting that p92 acts as a transcr iption factor, We have identified a class of nuclear inhibitory protei ns, I-92s, which noncovalently associate with p92 but not with other t ranscription factors such as AP1, E2F, or NF-KB. Different I-92s occur in G(1), G(2), and G(0), while no I-92 is detectable in S phase. Phas e-specific inhibitors, therefore, are responsible for the cell cycle d ependence of p92 activity and provide a novel mechanism linking transc ription factor regulation with the cell cycle.