Axin, an inhibitor of the Wnt signalling pathway, interacts with β-catenin, GSK-3β and APC and reduces the β-catenin level

被引:259
作者
Nakamura, T
Hamada, F
Ishidate, T
Anai, K
Kawahara, K
Toyoshima, K
Akiyama, T
机构
[1] Osaka Univ, Dept Oncogene Res, Inst Microbial Dis, Suita, Osaka 565, Japan
[2] Univ Tokyo, Inst Mol & Cellular Biosci, Dept Mol & Genet Informat, Bunkyo Ku, Tokyo 113, Japan
[3] Osaka Med Ctr Canc & Cardiovasc Dis, Higashinari Ku, Osaka 537, Japan
[4] JST, PRESTO, Tokyo, Japan
关键词
D O I
10.1046/j.1365-2443.1998.00198.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background: The Wnt/Wingless signalling pathway plays an important role in both embryonic development and tumorigenesis. beta-Catenin and Axin are positive and negative effectors of the Wnt signalling pathway, respectively. Results: We found that Axin interacts with beta-catenin and glycogen synthase kinase-3 beta (GSK-3 beta). Furthermore, the regulation of the G-protein signalling (RGS) domain of Axin is associated with the colorectal tumour suppressor adenomatous polyposis coli (APC). Overexpression of Axin in the human colorectal cancer cell line SW480 induced a drastic reduction in the level of beta-catenin. Interaction with beta-catenin and GSK-3 beta was required for the Axin-mediated beta-catenin reduction. Conclusion: Axin interacts with beta-catenin, GSK-3 beta and APC, and negatively regulates the Wnt signalling pathway, presumably by regulating the level of beta-catenin.
引用
收藏
页码:395 / 403
页数:9
相关论文
共 46 条
  • [1] beta-catenin is a target for the ubiquitin-proteasome pathway
    Aberle, H
    Bauer, A
    Stappert, J
    Kispert, A
    Kemler, R
    [J]. EMBO JOURNAL, 1997, 16 (13) : 3797 - 3804
  • [2] THE TUMOR-SUPPRESSOR GENE-PRODUCT APC BLOCKS CELL-CYCLE PROGRESSION FROM G(0)/G(1) TO S-PHASE
    BAEG, GH
    MATSUMINE, A
    KURODA, T
    BHATTACHARJEE, RN
    MIYASHIRO, I
    TOYOSHIMA, K
    AKIYAMA, T
    [J]. EMBO JOURNAL, 1995, 14 (22) : 5618 - 5625
  • [3] Functional interaction of an axin homolog, conductin, with β-catenin, APC, and GSK3β
    Behrens, J
    Jerchow, BA
    Würtele, M
    Grimm, J
    Asbrand, C
    Wirtz, R
    Kühl, M
    Wedlich, D
    Birchmeier, W
    [J]. SCIENCE, 1998, 280 (5363) : 596 - 599
  • [4] Functional interaction of beta-catenin with the transcription factor LEF-1
    Behrens, J
    vonKries, JP
    Kuhl, M
    Bruhn, L
    Wedlich, D
    Grosschedl, R
    Birchmeier, W
    [J]. NATURE, 1996, 382 (6592) : 638 - 642
  • [5] Wnt signaling: a common theme in animal development
    Cadigan, KM
    Nusse, R
    [J]. GENES & DEVELOPMENT, 1997, 11 (24) : 3286 - 3305
  • [6] Wingless inactivates glycogen synthase kinase-3 via an intracellular signalling pathway which involves a protein kinase C
    Cook, D
    Fry, MJ
    Hughes, K
    Sumathipala, R
    Woodgett, JR
    Dale, TC
    [J]. EMBO JOURNAL, 1996, 15 (17) : 4526 - 4536
  • [7] Structure and functions of the 20S and 26S proteasomes
    Coux, O
    Tanaka, K
    Goldberg, AL
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 1996, 65 : 801 - 847
  • [8] GAIP, A PROTEIN THAT SPECIFICALLY INTERACTS WITH THE TRIMERIC G-PROTEIN G-ALPHA(I3), IS A MEMBER OF A PROTEIN FAMILY WITH A HIGHLY CONSERVED CORE DOMAIN
    DEVRIES, L
    MOUSLI, M
    WURMSER, A
    FARQUHAR, MG
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (25) : 11916 - 11920
  • [9] RGS proteins and signaling by heterotrimeric G proteins
    Dohlman, HG
    Thorner, J
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (07) : 3871 - 3874
  • [10] THE EFFECTS OF A LETHAL MUTATION RESPONSIBLE FOR DUPLICATIONS AND TWINNING IN MOUSE EMBRYOS
    GLUECKSOHNSCHOENHEIMER, S
    [J]. JOURNAL OF EXPERIMENTAL ZOOLOGY, 1949, 110 (01): : 47 - 76