PUMA induces the rapid apoptosis of colorectal cancer cells

被引:1145
作者
Yu, J [1 ]
Zhang, L [1 ]
Hwang, PM [1 ]
Kinzler, KW [1 ]
Vogelstein, B [1 ]
机构
[1] Johns Hopkins Med Inst, Grad Program Human Genet & Mol Biol, Div Cardiol, Johns Hopkins Oncol Ctr,Howard Hughes Med Inst, Baltimore, MD 21231 USA
关键词
D O I
10.1016/S1097-2765(01)00213-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Through global profiling of genes that were expressed soon after p53 expression, we identified a novel gene termed PUMA (p53 upregulated modulator of apoptosis). The protein encoded by PUMA was found to be exclusively mitochondrial and to bind to Bcl-2 and Bcl-X-L through a BH3 domain. Exogenous expression of PUMA resulted in an extremely rapid and profound apoptosis that occurred much earlier than that resulting from exogenous expression of p53. Based on its unique expression patterns, p53 dependence, and biochemical properties, PUMA may be a direct mediator of p53-associated apoptosis.
引用
收藏
页码:673 / 682
页数:10
相关论文
共 54 条
  • [1] The Bcl-2 protein family: Arbiters of cell survival
    Adams, JM
    Cory, S
    [J]. SCIENCE, 1998, 281 (5381) : 1322 - 1326
  • [2] SUPPRESSION OF HUMAN COLORECTAL-CARCINOMA CELL-GROWTH BY WILD-TYPE-P53
    BAKER, SJ
    MARKOWITZ, S
    FEARON, ER
    WILLSON, JKV
    VOGELSTEIN, B
    [J]. SCIENCE, 1990, 249 (4971) : 912 - 915
  • [3] Drosophila p53 binds a damage response element at the reaper locus
    Brodsky, MH
    Nordstrom, W
    Tsang, G
    Kwan, E
    Rubin, GM
    Abrams, JM
    [J]. CELL, 2000, 101 (01) : 103 - 113
  • [4] Disruption of p53 in human cancer cells alters the responses to therapeutic agents
    Bunz, F
    Hwang, PM
    Torrance, C
    Waldman, T
    Zhang, YG
    Dillehay, L
    Williams, J
    Lengauer, C
    Kinzler, KW
    Vogelstein, B
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (03) : 263 - 269
  • [5] Requirement for p53 and p21 to sustain G2 arrest after DNA damage
    Bunz, F
    Dutriaux, A
    Lengauer, C
    Waldman, T
    Zhou, S
    Brown, JP
    Sedivy, JM
    Kinzler, KW
    Vogelstein, B
    [J]. SCIENCE, 1998, 282 (5393) : 1497 - 1501
  • [6] 14-3-3σ is required to prevent mitotic catastrophe after DNA damage
    Chan, TA
    Hermeking, H
    Lengauer, C
    Kinzler, KW
    Vogelstein, B
    [J]. NATURE, 1999, 401 (6753) : 616 - 620
  • [7] p53 transcriptional activity is essential for p53-dependent apoptosis following DNA damage
    Chao, C
    Saito, S
    Kang, J
    Anderson, CW
    Appella, E
    Xu, Y
    [J]. EMBO JOURNAL, 2000, 19 (18) : 4967 - 4975
  • [8] A CONSERVED DOMAIN IN BAK, DISTINCT FROM BH1 AND BH2, MEDIATES CELL-DEATH AND PROTEIN-BINDING FUNCTIONS
    CHITTENDEN, T
    FLEMINGTON, C
    HOUGHTON, AB
    EBB, RG
    GALLO, GJ
    ELANGOVAN, B
    CHINNADURAI, G
    LUTZ, RJ
    [J]. EMBO JOURNAL, 1995, 14 (22) : 5589 - 5596
  • [9] CRYSTAL-STRUCTURE OF A P53 TUMOR-SUPPRESSOR DNA COMPLEX - UNDERSTANDING TUMORIGENIC MUTATIONS
    CHO, YJ
    GORINA, S
    JEFFREY, PD
    PAVLETICH, NP
    [J]. SCIENCE, 1994, 265 (5170) : 346 - 355
  • [10] Regulation of p53 downstream genes
    El-Deiry, WS
    [J]. SEMINARS IN CANCER BIOLOGY, 1998, 8 (05) : 345 - 357