DIFFERENTIAL MODULATION OF CYCLIN GENE-EXPRESSION BY MYC

We have investigated the effects of deregulated expression of the huma n c-MYC protooncogene on cyclin gene expression and on the transcripti on factor E2F. We found that constitutive expression of MYC or activat ion of conditional MycER chimeras led to higher levels of cyclin A and cyclin E mRNA. Activation of cyclin A expression by MYC led to a grow th factor-independent association of cyclin A and cdk2 with the transc ription factor E2F and correlated with an increase in E2F transcriptio nal activity. In contrast, expression of the G1 phase cyclin D1 was st rongly reduced in MYC-transformed cells. In synchronized cells, repres sion of cyclin D1 by MYC occurred very early in the G1 phase of the ce ll cycle.