What are the mechanisms used by retroviruses to activate c-Myc expression?
Retroviruses can activate c-Myc oncogene expression in at least three ways: (1) use of virally encoded proteins to activate c-Myc transcription, (2) transduction and modification of the c-Myc gene to make a virally encoded form of the gene, and (3) cis-activation of c-Myc expression after proviral insertion. In the first method, there is evidence that some non-acute retroviruses encode factors that activate oncogene transcription in trans. HTLV-I, which induces human adult T cell leukemias, encodes a 40 kDa protein, Tax, that participates in T cell immortalization.37,38 Tax activates the expression of several transcription factors, including NF-B39,40,41 and CREB/ATF, that apparently bind to regulatory sites within the murine c-Myc locus.42 Mice that are bitransgenic for HTLV-I LTR-c-myc and immunoglobulin-Tax develop brain tumors and lymphomas, whereas the single-transgenic strains do not, suggesting that high-level Tax expression is necessary to get levels of c-Myc needed for lymphom
