TIN2, a new regulator of telomere length in human cells

被引:417
作者
Kim, SH [1 ]
Kaminker, P [1 ]
Campisi, J [1 ]
机构
[1] Lawrence Berkeley Natl Lab, Dept Cell & Mol Biol, Berkeley, CA 94720 USA
关键词
D O I
10.1038/70508
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Telomeres are DNA-protein structures that cap linear chromosomes and are essential for maintaining genomic stability and cell phenotype. We identified a novel human telomere-associated protein, TIN2, by interaction cloning using the telomeric DNA-binding-protein TRF1 as a bait. TIN2 interacted with TRF1 in vitro and in cells, and colocalized with TRF1 in nuclei and metaphase chromosomes. A mutant TIN2 that lacks amino-terminal sequences effects elongated human telomeres in a telomerase-dependent manner. Our findings suggest that TRF1 is insufficient for control of telomere length in human cells, and that TIN2 is an essential mediator of TRF1 function.
引用
收藏
页码:405 / 412
页数:8
相关论文
共 47 条
  • [1] MODIFIERS OF POSITION EFFECT ARE SHARED BETWEEN TELOMERIC AND SILENT MATING-TYPE LOCI IN SACCHAROMYCES-CEREVISIAE
    APARICIO, OM
    BILLINGTON, BL
    GOTTSCHLING, DE
    [J]. CELL, 1991, 66 (06) : 1279 - 1287
  • [2] STRUCTURE AND FUNCTION OF TELOMERES
    BLACKBURN, EH
    [J]. NATURE, 1991, 350 (6319) : 569 - 573
  • [3] Extension of life-span by introduction of telomerase into normal human cells
    Bodnar, AG
    Ouellette, M
    Frolkis, M
    Holt, SE
    Chiu, CP
    Morin, GB
    Harley, CB
    Shay, JW
    Lichtsteiner, S
    Wright, WE
    [J]. SCIENCE, 1998, 279 (5349) : 349 - 352
  • [4] Mechanism of telomerase induction during T cell activation
    Bodnar, AG
    Kim, NW
    Effros, RB
    Chiu, CP
    [J]. EXPERIMENTAL CELL RESEARCH, 1996, 228 (01) : 58 - 64
  • [5] THE SIR2 GENE FAMILY, CONSERVED FROM BACTERIA TO HUMANS, FUNCTIONS IN SILENCING, CELL-CYCLE PROGRESSION, AND CHROMOSOME STABILITY
    BRACHMANN, CB
    SHERMAN, JM
    DEVINE, SE
    CAMERON, EE
    PILLUS, L
    BOEKE, JD
    [J]. GENES & DEVELOPMENT, 1995, 9 (23) : 2888 - 2902
  • [6] A NEW DIPLOID NONTUMORIGENIC HUMAN-BREAST EPITHELIAL-CELL LINE ISOLATED AND PROPAGATED IN CHEMICALLY DEFINED MEDIUM
    BRIAND, P
    PETERSEN, OW
    VANDEURS, B
    [J]. IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY, 1987, 23 (03): : 181 - 188
  • [7] Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines
    Bryan, TM
    Englezou, A
    DallaPozza, L
    Dunham, MA
    Reddel, RR
    [J]. NATURE MEDICINE, 1997, 3 (11) : 1271 - 1274
  • [8] Telomerase regulation during entry into the cell cycle in normal human T cells
    Buchkovich, KJ
    Greider, CW
    [J]. MOLECULAR BIOLOGY OF THE CELL, 1996, 7 (09) : 1443 - 1454
  • [9] The biology of replicative senescence
    Campisi, J
    [J]. EUROPEAN JOURNAL OF CANCER, 1997, 33 (05) : 703 - 709
  • [10] Campisi Judith, 1996, P121