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Out with the active ß-catenin

A highly active subset of ß-catenin is specifically expelled from the nucleus by RanBP3, according to Hendriksen et al. on page 785. This active pool is just a tiny fraction of total ß-catenin, but should be the focus of future studies on Wnt signaling.

Wnt signals are converted into changes in gene expression by ß-catenin, which turns on the TCF/Lef transcription factors. In a search for nuclear ß-catenin–interacting proteins, the authors picked up RanBP3 in a pull-down assay. As RanBP3 is a cofactor for CRM1-mediated nuclear export, the logical next step was to look at ß-catenin export.

Nuclear levels of total ß-catenin were not affected by RanBP3, but the authors found a more specific target. A very small, almost invisible, fraction of ß-catenin—the active dephosporylated form—relocated from the nucleus to the cytoplasm upon RanBP3 overexpression. Only by using tumor cell lines with unusually high levels of active ß-catenin were the authors even able to detect this pool in situ.

As a result of the export, Wnt signals were unable to activate their transcription programs. By contrast, fly embryos lacking active RanBP3 had developmental defects associated with too much Wnt (presumably from too much active nuclear ß-catenin). RanBP3 overexpression in frog embryos had the reverse effect. The authors do not yet know whether endogenous RanBP3 levels increase to inhibit Wnt signaling, as required during differentiation, for example.

RanBP3 is a cofactor for the CRM1 exporter, but ß-catenin export was independent of CRM1. Perhaps RanBP3 accompanies ß-catenin through a different export pathway. Alternatively, RanBP3 might compete for DNA binding sites that retain active ß-catenin in the nucleus.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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RanBP3 enhances nuclear export of active ß-catenin independently of CRM1

Jolita Hendriksen, Francois Fagotto, Hella van der Velde, Martijn van Schie, Jasprien Noordermeer, and Maarten Fornerod
J. Cell Biol. 2005 171: 785-797. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 722K) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Article Social Bookmarking                            What's this?