UP-REGULATION OF C-MYC INDUCES THE GENE-EXPRESSION OF THE MURINE HOMOLOGS OF P34(CDC2) AND CYCLIN-DEPENDENT KINASE-2 IN T-LYMPHOCYTES

The expression and/or up-regulation of several early T cell activation genes is dependent on signals transmitted through the interaction of IL-2 and IL-2R well before entry of the cells into S phase. In these s tudies, murine G(0) T cells activated by immobilized anti-CD3 and subs equently blocked in late G(1) expressed normal surface levels and mRNA for IL-2 alpha, IL-2R beta, and transferrin receptor (TfR). However, there was no expression of p34(cdc2), and cyclin-dependent kinase (cdk )-2 was not up-regulated even in the presence of exogenous rIL-2. In a ddition the accumulation of c-myc-specific mRNA and protein was signif icantly reduced. Pretreatment of G(0) T cells with c-myc antisense oli gonucleotide effectively reduced the level of specific c-myc protein i nduced by activation of the cells by immobilized anti-CD3. The presenc e of antisense c-myc oligonucleotide inhibited the expression of cdc2 and cdk2 without affecting the expression of IL-2R alpha and blocked t he activated T cells in the G(1) phase. Together these studies demonst rate that c-myc regulates the expression of these cdk and suggest a ro le for c-myc in the G(1)/S transition.