Human T-cell lymphotropic virus type-1 (HTLV-1) infects and transforms CD4+ lymphocytes and causes Adult T-cell Leukemia/Lymphoma (ATLL), an aggressive, often fatal, lymphoproliferative disease. A conserved HTLV-1 3+ regulatory domain, pX, encodes at least five non-structural proteins, including the alternative splice-variant p30II. HTLV-1 p30II may enhance the transforming activity of Myc and transcriptionally activate the human cyclin D2 promoter, dependent upon its conserved Myc-responsive enhancer elements, associated with markedly increased S-phase entry and multi-nucleation. Enhancement of Myc transforming activity by HTLV-1 p30II may be dependent upon the transcriptional coactivators, TRRAP/p4346-8 and TIP60, require TIP60 histone acetyltransferase activity, and strongly correlate with interactions between HTLV-1 p30II and Myc-TIP60 complexes in HTLV-1-infected ATLL patient-derived lymphocytes. Thus, p30II may function as a novel retroviral modulator of Myc-transforming interactions that may prominently contribute to adult T-cell leukemogenesis. Thus, the present invention provides methods and compositions for screening and identifying agents that interfere with transformation.