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 human papillomavirus type 18 p92 binding sequence confers enhancer activity on a heterologous promoter, suggesting that p92 acts as a transcription factor, We have identified a class of nuclear inhibitory proteins, I-92s, which noncovalently associate with p92 but not with other transcription 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. Phase-specific inhibitors, therefore, are responsible for the cell cycle dependence of p92 activity and provide a novel mechanism linking transcription factor regulation with the cell cycle.