Telomerase regulation during entry into the cell cycle in normal human T cells.
Telomerase activity is involved in telomere length maintenance. Leukocytes, unlike many human somatic tissues, have detectable telomerase activity. These cells provide a normal human cell type in which to study telomerase. We studied the regulation of telomerase activity and the telomerase RNA component as leukocytes were stimulated to enter the cell cycle. In primary human leukocytes stimulated with phytohemagglutinin, telomerase activity increased > 10-fold as naturally quiescent cells entered the cell cycle. Antibodies to the T cell receptor (TCR)/CD3 complex and the costimulatory CD28 receptor induced telomerase activity in a T cell-enriched population of cells. Rapamycin, an immunosuppressant that blocks TCR/CD3 signal transduction pathways and cdk2 activation, blocked telomerase induction. Hydroxyurea, an inhibitor of S phase, did not block cdk2 kinase activity or telomerase activation. In summary, telomerase is regulated in G1 phase as normal human T cells enter the cell cycle.
Buchkovich
K J
KJ
Cold Spring Harbor Laboratory, New York 11724, USA.
Greider
C W
CW
D000906:Antibodies / Q000494:pharmacology; D018951:Antigens, CD20 / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology; D015152:Blotting, Northern; D018801:CD2 Antigens / Q000032:analysis; D018106:CD28 Antigens / Q000378:metabolism; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000187:drug effects / Q000378:metabolism; D016213:Cyclins / Q000096:biosynthesis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D011090:Polyenes / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D020123:Sirolimus; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D019098:Telomerase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
D000906:Antibodies; D018951:Antigens, CD20; D018801:CD2 Antigens; D018106:CD28 Antigens; D018797:Cell Cycle Proteins; D016213:Cyclins; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D008869:Microtubule-Associated Proteins; D010835:Phytohemagglutinins; D011090:Polyenes; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D012313:RNA; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D019098:Telomerase; D020123:Sirolimus; D006918:Hydroxyurea