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Suppressor of fused negatively regulates beta-catenin signaling.

Publication ,  Journal Article
Meng, X; Poon, R; Zhang, X; Cheah, A; Ding, Q; Hui, CC; Alman, B
Published in: J Biol Chem
October 26, 2001

Suppressor of fused (Su(fu)) is a negative regulator of the Hedgehog signaling pathway that controls the nuclear-cytoplasmic distribution of Gli/Ci transcription factors through direct protein-protein interactions. We show here that Su(fu) is present in a complex with the oncogenic transcriptional activator beta-catenin and functions as a negative regulator of T-cell factor (Tcf)-dependent transcription. Overexpression of Su(fu) in SW480 (APC(mut)) colon cancer cells in which beta-catenin protein is stabilized leads to a reduction in nuclear beta-catenin levels and in Tcf-dependent transcription. This effect of Su(fu) overexpression can be blocked by treatment of these cells with leptomycin B, a specific inhibitor of CRM1-mediated nuclear export. Overexpression of Su(fu) suppresses growth of SW480 (APC(mut)) tumor cells in nude mice. These observations indicate that Su(fu) negatively regulates beta-catenin signaling and that CRM-1-mediated nuclear export plays a role in this regulation. Our results also suggest that Su(fu) acts as a tumor suppressor.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

October 26, 2001

Volume

276

Issue

43

Start / End Page

40113 / 40119

Location

United States

Related Subject Headings

  • beta Catenin
  • Zebrafish Proteins
  • Wnt Proteins
  • Tumor Cells, Cultured
  • Transcription Factors
  • Trans-Activators
  • Suppressor Factors, Immunologic
  • Signal Transduction
  • Repressor Proteins
  • Receptors, Cytoplasmic and Nuclear
 

Citation

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Meng, X., Poon, R., Zhang, X., Cheah, A., Ding, Q., Hui, C. C., & Alman, B. (2001). Suppressor of fused negatively regulates beta-catenin signaling. J Biol Chem, 276(43), 40113–40119. https://doi.org/10.1074/jbc.M105317200
Meng, X., R. Poon, X. Zhang, A. Cheah, Q. Ding, C. C. Hui, and B. Alman. “Suppressor of fused negatively regulates beta-catenin signaling.J Biol Chem 276, no. 43 (October 26, 2001): 40113–19. https://doi.org/10.1074/jbc.M105317200.
Meng X, Poon R, Zhang X, Cheah A, Ding Q, Hui CC, et al. Suppressor of fused negatively regulates beta-catenin signaling. J Biol Chem. 2001 Oct 26;276(43):40113–9.
Meng, X., et al. “Suppressor of fused negatively regulates beta-catenin signaling.J Biol Chem, vol. 276, no. 43, Oct. 2001, pp. 40113–19. Pubmed, doi:10.1074/jbc.M105317200.
Meng X, Poon R, Zhang X, Cheah A, Ding Q, Hui CC, Alman B. Suppressor of fused negatively regulates beta-catenin signaling. J Biol Chem. 2001 Oct 26;276(43):40113–40119.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

October 26, 2001

Volume

276

Issue

43

Start / End Page

40113 / 40119

Location

United States

Related Subject Headings

  • beta Catenin
  • Zebrafish Proteins
  • Wnt Proteins
  • Tumor Cells, Cultured
  • Transcription Factors
  • Trans-Activators
  • Suppressor Factors, Immunologic
  • Signal Transduction
  • Repressor Proteins
  • Receptors, Cytoplasmic and Nuclear