Telomerase regulation during entry into the cell cycle in normal human T cells

被引:198
作者
Buchkovich, KJ [1 ]
Greider, CW [1 ]
机构
[1] COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724
关键词
D O I
10.1091/mbc.7.9.1443
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1443 / 1454
页数:12
相关论文
共 65 条
[1]  
AVILION AA, 1995, THESIS STATE U NEW Y
[2]  
BACCHETTI S, 1995, INT J ONCOL, V7, P423
[3]   FUNCTIONAL-CHARACTERIZATION AND DEVELOPMENTAL REGULATION OF MOUSE TELOMERASE RNA [J].
BLASCO, MA ;
FUNK, W ;
VILLEPONTEAU, B ;
GREIDER, CW .
SCIENCE, 1995, 269 (5228) :1267-1270
[4]   TELOMERASE ACTIVITY IN NORMAL AND MALIGNANT HEMATOPOIETIC-CELLS [J].
BROCCOLI, D ;
YOUNG, JW ;
DELANGE, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (20) :9082-9086
[5]   NERVE GROWTH-FACTOR REGULATES THE EXPRESSION AND ACTIVITY OF P33(CDK2) AND P34(CDC2) KINASES IN PC12 PHEOCHROMOCYTOMA CELLS [J].
BUCHKOVICH, KJ ;
ZIFF, EB .
MOLECULAR BIOLOGY OF THE CELL, 1994, 5 (11) :1225-1241
[6]   THE 70-KDA S6-KINASE - REGULATION OF A KINASE WITH MULTIPLE ROLES IN MITOGENIC SIGNALING [J].
CHOU, MM ;
BLENIS, J .
CURRENT OPINION IN CELL BIOLOGY, 1995, 7 (06) :806-814
[7]   TELOMERASE IN YEAST [J].
COHN, M ;
BLACKBURN, EH .
SCIENCE, 1995, 269 (5222) :396-400
[8]   TELOMERASE ACTIVITY IN NORMAL LEUKOCYTES AND IN HEMATOLOGIC MALIGNANCIES [J].
COUNTER, CM ;
GUPTA, J ;
HARLEY, CB ;
LEBER, B ;
BACCHETTI, S .
BLOOD, 1995, 85 (09) :2315-2320
[9]   TELOMERE SHORTENING ASSOCIATED WITH CHROMOSOME INSTABILITY IS ARRESTED IN IMMORTAL CELLS WHICH EXPRESS TELOMERASE ACTIVITY [J].
COUNTER, CM ;
AVILION, AA ;
LEFEUVRE, CE ;
STEWART, NG ;
GREIDER, CW ;
HARLEY, CB ;
BACCHETTI, S .
EMBO JOURNAL, 1992, 11 (05) :1921-1929
[10]   STABILIZATION OF SHORT TELOMERES AND TELOMERASE ACTIVITY ACCOMPANY IMMORTALIZATION OF EPSTEIN-BARR VIRUS-TRANSFORMED HUMAN B-LYMPHOCYTES [J].
COUNTER, CM ;
BOTELHO, FM ;
WANG, P ;
HARLEY, CB ;
BACCHETTI, S .
JOURNAL OF VIROLOGY, 1994, 68 (05) :3410-3414