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Nuclear targeting of beta-catenin is an obligatory step in Wnt signal transduction, but the factors that control import and export remain to be clarified. In this issue, Hendriksen et al. (p. 785) show that the RanBP3 export factor antagonizes beta-catenin/T cell factor (TCF) transcription by targeting the signaling-competent form of beta-catenin. We speculate that cells may use multiple export mechanisms to inhibit beta-catenin signaling in different ways.
Figure 1. RanBP3 promotes export of activated β-catenin. During Wnt signaling, the Axin–GSK3β–APC phosphorylation/predestruction complex is inactivated and leads to cytosolic accumulation of a form of β-catenin that is unphosphorylated at GSK3β-dependent serines 37 and 41. This “activated” form is then available to enter the nucleus and participate as a coactivator for the transcription of TCF target genes. Data presented by Hendriksen et al. (2005) supports a model in which this activated form of β-catenin is exported from the nucleus by RanBP3 in a RanGTP-dependent manner. Cytosolic Ran GTPase-activating proteins promote GTP hydrolysis and presumably release the active form of β-catenin in the cytosol.
Figure 2. Distinct modes of β-catenin nuclear export. APC-directed export of β-catenin may be coupled to degradation, whereas RanBP3-directed export may allow for cycles of export and reimport. See text for details.
DasGupta,
Functional genomic analysis of the Wnt-wingless signaling pathway.
2005, Pubmed
DasGupta,
Functional genomic analysis of the Wnt-wingless signaling pathway.
2005,
Pubmed
Englmeier,
RanBP3 influences interactions between CRM1 and its nuclear protein export substrates.
2001,
Pubmed
Guger,
A mode of regulation of beta-catenin signaling activity in Xenopus embryos independent of its levels.
2000,
Pubmed
,
Xenbase
Hart,
The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell.
1999,
Pubmed
Henderson,
The ins and outs of APC and beta-catenin nuclear transport.
2002,
Pubmed
Hendriksen,
RanBP3 enhances nuclear export of active (beta)-catenin independently of CRM1.
2005,
Pubmed
,
Xenbase
Ikeda,
Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin.
1998,
Pubmed
Liu,
Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism.
2002,
Pubmed
,
Xenbase
Sadot,
Regulation of S33/S37 phosphorylated beta-catenin in normal and transformed cells.
2002,
Pubmed
Staal,
Wnt signals are transmitted through N-terminally dephosphorylated beta-catenin.
2002,
Pubmed
Wiechens,
CRM1- and Ran-independent nuclear export of beta-catenin.
2001,
Pubmed
,
Xenbase
Yost,
The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3.
1996,
Pubmed
,
Xenbase
