Up-regulation of c-myc induces the gene expression of the murine homologues of p34cdc2 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 studies, murine G0 T cells activated by immobilized anti-CD3 and subsequently blocked in late G1 expressed normal surface levels and mRNA for IL-2R alpha, IL-2R beta, and transferrin receptor (TfR). However, there was no expression of p34cdc2, and cyclin-dependent kinase (cdk)-2 was not up-regulated even in the presence of exogenous rIL-2. In addition the accumulation of c-myc-specific mRNA and protein was significantly reduced. Pretreatment of G0 T cells with c-myc antisense oligonucleotide effectively reduced the level of specific c-myc protein induced by activation of the cells by immobilized anti-CD3. The presence of antisense c-myc oligonucleotide inhibited the expression of cdc2 and cdk2 without affecting the expression of IL-2R alpha and blocked the activated T cells in the G1 phase. Together these studies demonstrate that c-myc regulates the expression of these cdk and suggest a role for c-myc in the G1/S transition.
Kim
Y H
YH
Clinical Immunology Section, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
Buchholz
M A
MA
Chrest
F J
FJ
Nordin
A A
AA
D000818:Animals; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000235:genetics*; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D016259:Genes, myc; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D013844:Thiazoles / Q000494:pharmacology; D015854:Up-Regulation
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D013844:Thiazoles; C063742:HOE 768159; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases