O-17 Viruses have long been used to understand various basic cellular machineries, including transcription and the cell cycle. Recently it has been shown that HTLV-1 and/or Tax1 expressing cells have altered gene expression of some cell cycle associated genes Among these changes, high levels of p53, cdk inhibitor p21. Cyclin D2, and cdk inhibitor p16 have been observed. All of these changes are associated with the GI phase of the cell cycle. The Gl phase is normally divided into G1pm (GI post mitosis), "R" (Time point where Rb is phosphorylated), and G1ps (GI pre-S phase). Two proteins control the G1 phase: Rb, which acts as a transcriptional co-repressor; and CBP/P300 which a transcriptional co-activator. In HTLV-1 infected patient samples, as well as in cell lines, we find that at the G1pm phase, the Cyclin D2 promoter is up-regulated by Tax, though a CRE clement in the Cyclin D2 promoter. In transient transfection assays, the CRE element binds to CREB and is responsive to wild type, but not M47 Tax mutant. The functional consequence of up-regulation of this Cyclin is phosphorylation of Rb protein at "R" time point. At the G1ps, we find that cyclin E associated complexes are active in the HTLV-1 infected samples and that it phosphorylates substrates other than histone H1 or Rb. In vitro experiments using purified recombinant proteins indicates that Cyclin E-Cdk2 complexes from HTLV-1 infected cells can specifically phosphorylate CBP. Analysis of four CBS and three p300 deletion mutants suggests that CBP phosphorylation by cyclin E-Cdk2 occurs in the carboxy-terminal region. Treatment of recombinant CBP with purified Cyclin E-Cdk2 in vitro causes HAT (histone acetyl transferase) activity of CBP to increase, In infected cells, CBP- associated HAT activity increases sharply at 6-7 hrs post G0(serum starvation) release, whereas in uninfected cells it increases later at 9-10 hours. The increase in HAT activity can be demonstrated by both histone acetylation in a filter binding assay as well as with an in vitro chromatin remodeling assay on the Cyclin A promoter. The functional consequence of the CBP phosphorylation and increased HAT activity in HTLV-1 infected cells is the shortening of the G1ps phase as demonstrated by the rapid appearance of G1ps markers namely Cyclin A and PCNA proteins. Therefore, we propose that specific events during the G1 phase, such as Rb and CBP phosphorylation, allow shortening of the G1 phase and a premature entry into S phase. These events are hallmarks of loss of the G1/S check point.