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β-catenin inhibits promyelocytic leukemia protein tumor suppressor function in colorectal cancer cells.

BACKGROUND & AIMS: Loss of promyelocytic leukemia protein (PML) nuclear body (NB) formation has been reported in colorectal and other solid tumors. However, genetic alteration of PML is rarely observed in these tumors; the exact mechanisms that mediate loss of PML function are not known. METHODS: We previously used a comprehensive shotgun mass spectrometry approach to identify PML as 1 of 70 proteins that coimmunoprecipitate with anti-T-cell factor 4 in DLD-1 and HCT116 colorectal cancer cell lines; we investigated the effects of altered β-catenin expression on PML function in these cells. RESULTS: β-catenin specifically interacted with the product of PML transcript variant IV (PML-IV) through the armadillo repeat domain of β-catenin. Overexpression of β-catenin in colorectal cancer cells disrupted the subcellular compartmentalization of PML-IV, whereas knockdown of β-catenin restored formation of PML-NB. Modification of PML by the small ubiquitin-related modifier (SUMO) is required for proper assembly of PML-NB. β-catenin inhibited Ran-binding protein 2-mediated SUMOylation of PML-IV. CONCLUSIONS: β-catenin interacts with PML isoform IV and disrupts PML-IV function and PML-NB formation by inhibiting Ran-binding protein 2-mediated SUMO modification of PML-IV. These findings indicate the involvement of a posttranslational mechanism in disruption of PML-NB organization in cancer cells and provide more information about the oncogenic functions of β-catenin.

Pubmed ID: 22155184

Authors

  • Satow R
  • Shitashige M
  • Jigami T
  • Fukami K
  • Honda K
  • Kitabayashi I
  • Yamada T

Journal

Gastroenterology

Publication Data

March 27, 2012

Associated Grants

None

Mesh Terms

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cell Nucleus
  • Colorectal Neoplasms
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Lysine
  • Molecular Chaperones
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • Protein Binding
  • Protein Isoforms
  • RNA Interference
  • Small Ubiquitin-Related Modifier Proteins
  • Sumoylation
  • Transcription Factors
  • Transcriptional Activation
  • Transfection
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Wnt Signaling Pathway
  • beta Catenin