The regulation of p27Kip1 expression following the polyclonal activation of murine G0 T cells.
Polyclonal activation of murine G0 T cells with immobilized anti-CD3 induces entry into the cell cycle as well as the subsequent cytokine-dependent proliferative response. G0 T cells express high levels of p27Kip1 protein and specific mRNA, which decline rapidly following activation. The decline in the expression of p27Kip1 and sequestering of the inhibitory protein by cdk4 and cdk6 correlated with the increase in cdk2 kinase activity during the G1 phase. Anti-CD3 activation of G0 T cells in the presence of cyclosporin A or rapamycin inhibited the down-regulation of p27Kip1, the cellular levels of the inhibitor remained high, and the cells remained in the G1 phase. PBu2 activation of G0 T cells also did not result in the down-regulation of p27Kip1 and the cells remained in G1. In each instance IL-2 restored the down-regulation of p27Kip1, resulting in a significant reduction in the level of the inhibitor, and stimulated the cells to progress through the cell cycle. Jurkat cells transfected with the p27GL-988 plasmid containing +1 to -988 nt of the p27Kip1 promoter region and subsequently exposed to rIL-2 resulted in a significant reduction in the activity of the p27Kip1 promoter. These findings suggest that in addition to providing the signals required for activated T cells to traverse G1/S, IL-2 also influences the promoter function of p27Kip1, which effectively induces transcriptional down-regulation of the gene.
Kwon
T K
TK
Laboratory of Clinical Physiology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Buchholz
M A
MA
Ponsalle
P
P
Chrest
F J
FJ
Nordin
A A
AA
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D042846:CDC2-CDC28 Kinases; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015536:Down-Regulation; D007376:Interleukin-2 / Q000502:physiology; D007399:Interphase; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D025521:Tumor Suppressor Proteins
D017252:CD3 Complex; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D007376:Interleukin-2; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases