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HDAC6 is required for epidermal growth factor-induced beta-catenin nuclear localization.

Publication ,  Journal Article
Li, Y; Zhang, X; Polakiewicz, RD; Yao, T-P; Comb, MJ
Published in: J Biol Chem
May 9, 2008

Nuclear translocation of beta-catenin is a hallmark of Wnt signaling and is associated with various cancers. In addition to the canonical Wnt pathway activated by Wnt ligands, growth factors such as epidermal growth factor (EGF) also induce beta-catenin dissociation from the adherens junction complex, translocation into the nucleus, and activation of target genes such as c-myc. Here we report that EGF-induced beta-catenin nuclear localization and activation of c-myc are dependent on the deacetylase HDAC6. We show that EGF induces HDAC6 translocation to the caveolae membrane and association with beta-catenin. HDAC6 deacetylates beta-catenin at lysine 49, a site frequently mutated in anaplastic thyroid cancer, and inhibits beta-catenin phosphorylation at serine 45. HDAC6 inactivation blocks EGF-induced beta-catenin nuclear localization and decreases c-Myc expression, leading to inhibition of tumor cell proliferation. These results suggest that EGF-induced nuclear localization of beta-catenin is regulated by HDAC6-dependent deacetylation and provide a new mechanism by which HDAC inhibitors prevent tumor growth.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

May 9, 2008

Volume

283

Issue

19

Start / End Page

12686 / 12690

Location

United States

Related Subject Headings

  • beta Catenin
  • Sequence Alignment
  • Protein Binding
  • Phosphorylation
  • Molecular Sequence Data
  • Humans
  • Histone Deacetylases
  • Histone Deacetylase 6
  • Epidermal Growth Factor
  • Enzyme Activation
 

Citation

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MLA
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Li, Y., Zhang, X., Polakiewicz, R. D., Yao, T.-P., & Comb, M. J. (2008). HDAC6 is required for epidermal growth factor-induced beta-catenin nuclear localization. J Biol Chem, 283(19), 12686–12690. https://doi.org/10.1074/jbc.C700185200
Li, Yu, Xiaowu Zhang, Roberto D. Polakiewicz, Tso-Pang Yao, and Michael J. Comb. “HDAC6 is required for epidermal growth factor-induced beta-catenin nuclear localization.J Biol Chem 283, no. 19 (May 9, 2008): 12686–90. https://doi.org/10.1074/jbc.C700185200.
Li Y, Zhang X, Polakiewicz RD, Yao T-P, Comb MJ. HDAC6 is required for epidermal growth factor-induced beta-catenin nuclear localization. J Biol Chem. 2008 May 9;283(19):12686–90.
Li, Yu, et al. “HDAC6 is required for epidermal growth factor-induced beta-catenin nuclear localization.J Biol Chem, vol. 283, no. 19, May 2008, pp. 12686–90. Pubmed, doi:10.1074/jbc.C700185200.
Li Y, Zhang X, Polakiewicz RD, Yao T-P, Comb MJ. HDAC6 is required for epidermal growth factor-induced beta-catenin nuclear localization. J Biol Chem. 2008 May 9;283(19):12686–12690.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

May 9, 2008

Volume

283

Issue

19

Start / End Page

12686 / 12690

Location

United States

Related Subject Headings

  • beta Catenin
  • Sequence Alignment
  • Protein Binding
  • Phosphorylation
  • Molecular Sequence Data
  • Humans
  • Histone Deacetylases
  • Histone Deacetylase 6
  • Epidermal Growth Factor
  • Enzyme Activation