IQGAP1-mediated Stimulation of Transcriptional Co-activation by β-Catenin Is Modulated by Calmodulin*

β-Catenin, an oncoprotein integral to cell-cell adhesion and proliferative signaling, is increased in several malignancies. The recently discovered calmodulin-binding protein IQGAP1 binds stoichiometrically to β-catenin and regulates the association of β-catenin with the cell-cell adhesion complex. In the present work, we investigated the role of IQGAP1 on the transcriptional co-activator function of β-catenin, and whether calmodulin modulated the functional interaction between IQGAP1 and β-catenin. In vitro competition assays revealed that both Ca2+/calmodulin and apo-calmodulin, when pre-bound to IQGAP1, prevented binding of β-catenin to IQGAP1, and partially displaced β-catenin pre-bound to IQGAP1 when added subsequently. Conversely, β-catenin partially displaced apo-calmodulin, but not Ca2+/calmodulin, from IQGAP1. Overexpression of IQGAP1 in SW480 colon carcinoma cells enhanced β-catenin-mediated transcriptional co-activation by 1.72-fold, and this stimulation was significantly attenuated upon antagonism of calmodulin using the cell-permeable antagonist CGS9343B. Moreover, an IQGAP1 mutant that does not bind calmodulin was unable to stimulate β-catenin transcriptional function. Results of pulse-chase analyses suggested that IQGAP1 slowed the turnover of soluble, but not total, β-catenin. Immunocytochemistry revealed that IQGAP1 overexpression increased the amount of β-catenin located in the nucleus, whereas incubation of cells with CGS9343B blocked this accumulation. Together, our results imply that IQGAP1 enhances the function of β-catenin in the nucleus and that calmodulin regulates this stimulation.

• Publication year

  2002

• Venue

  Journal of Biological Chemistry

• Publication date

  2002-03-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.M104315200PMID 11734550
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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