Skip NavigationSkip to Content
Return Return to Search Results

A Novel Wilms Tumor 1 (WT1) Target Gene Negatively Regulates the WNT Signaling Pathway

  1. Author:
    Kim, M. S.
    Yoon, S. K.
    Bollig, F.
    Kitagaki, J.
    Hur, W.
    Whye, N. J.
    Wu, Y. P.
    Rivera, M. N.
    Park, J. Y.
    Kim, H. S.
    Malik, K.
    Bell, D. W.
    Englert, C.
    Perantoni, A. O.
    Lee, S. B.

  2. Author Address

    [Kim, Myoung Shin; Whye, Nathan J.; Wu, Yun-Ping; Park, Jik Young; Kim, Ho-Shik; Lee, Sean Bong] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Yoon, Seung Kew; Hur, Wonhee] Catholic Univ Korea, Dept Internal Med, World Hlth Org,Catholic Res Inst Med Sci, Collaborating Ctr Viral Hepatitis, Seoul 137701, South Korea. [Bollig, Frank; Englert, Christoph] Fritz Lipmann Inst, Leibniz Inst Age Res, D-07745 Jena, Germany. [Kitagaki, Jirouta; Perantoni, Alan O.] NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21702 USA. [Rivera, Miguel N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. [Malik, Karim] Univ Bristol, Canc & Leukaemia Childhood Sargent Unit, Dept Cellular & Mol Med, Bristol BS8 1TD, Avon, England. [Bell, Daphne W.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.;Lee, SB, NIDDK, Genet Dev & Dis Branch, NIH, 9000 Rockville Pike,Bldg 10,9D11, Bethesda, MD 20892 USA.;seanL@mail.nih.gov
    1. Year: 2010
    2. Date: May
  2. Journal: Journal of Biological Chemistry
    1. 285
    2. 19
    3. Pages: 14585-14593
  4. Type of Article: Article
  5. ISSN: 0021-9258
  1. Abstract:

    Mammalian kidney development requires the functions of the Wilms tumor gene WT1 and the WNT/beta-catenin signaling pathway. Recent studies have shown that WT1 negatively regulates WNT/beta-catenin signaling, but the molecular mechanisms by which WT1 inhibits WNT/beta-catenin signaling are not completely understood. In this study, we identified a gene, CXXC5, which we have renamed WID (WT1-induced Inhibitor of Dishevelled), as a novel WT1 transcriptional target that negatively regulates WNT/beta-catenin signaling. WT1 activates WID transcription through the upstream enhancer region. In the developing kidney, Wid and Wt1 are coexpressed in podocytes of maturing nephrons. Structure-function analysis demonstrated that WID interacts with Dishevelled via its C-terminal CXXC zinc finger and Dishevelled binding domains and potently inhibits WNT/beta-catenin signaling in vitro and in vivo. WID is evolutionarily conserved, and ablation of wid in zebrafish embryos with antisense morpholino oligonucleotides perturbs embryonic kidney development. Taken together, our results demonstrate that the WT1 negatively regulates WNT/beta-catenin pathway via its target gene WID and further suggest a role for WID in nephrogenesis.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1074/jbc.M109.094334
  3. View record in Web of Science®
  4. WOS: 000277299700055

Library Notes

  1. Fiscal Year: FY2009-2010
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel