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Terminating Wnt signals: a novel nuclear export mechanism targets activated (beta)-catenin.

Thorne ME, Gottardi CJ - J. Cell Biol. (2005)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Northwestern University, Chicago, IL 60637, USA.

ABSTRACT
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.

Show MeSH
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.
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fig2: 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.

Mentions: Currently there are two models for nuclear export of β-catenin, one in which β-catenin directly engages the nuclear pore complex for export, and the other a CRM1-dependent pathway that relies on nuclear export sequences provided by another carrier, such as APC (for review see Henderson and Fagotto, 2002). Because Hendriksen et al. (2005) demonstrate that RanBP3 exports β-catenin independent of APC and CRM1, this suggests a third mechanism for nuclear export. Why might the cell use so many different modes of β-catenin export? Perhaps different modes of export could allow for different degrees of signaling inhibition (Fig. 2). For example, APC-mediated export may couple nuclear exit with degradation, irreversibly inhibiting the pathway. This export mechanism may predominate in the absence of Wnts or under conditions where a pulse of Wnt signaling must be rapidly diminished. On the other hand, RanBP3-dependent export may be less coordinated with cytoplasmic degradation, and thus this mechanism may predominate during times of more sustained Wnt activation. How these different export mechanisms are calibrated to generate different levels and durations of Wnt signals is currently unclear, but Hendriksen et al. (2005) have provided us with new insights into the regulation of β-catenin nuclear export.


Terminating Wnt signals: a novel nuclear export mechanism targets activated (beta)-catenin.

Thorne ME, Gottardi CJ - J. Cell Biol. (2005)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171287&req=5

fig2: 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.
Mentions: Currently there are two models for nuclear export of β-catenin, one in which β-catenin directly engages the nuclear pore complex for export, and the other a CRM1-dependent pathway that relies on nuclear export sequences provided by another carrier, such as APC (for review see Henderson and Fagotto, 2002). Because Hendriksen et al. (2005) demonstrate that RanBP3 exports β-catenin independent of APC and CRM1, this suggests a third mechanism for nuclear export. Why might the cell use so many different modes of β-catenin export? Perhaps different modes of export could allow for different degrees of signaling inhibition (Fig. 2). For example, APC-mediated export may couple nuclear exit with degradation, irreversibly inhibiting the pathway. This export mechanism may predominate in the absence of Wnts or under conditions where a pulse of Wnt signaling must be rapidly diminished. On the other hand, RanBP3-dependent export may be less coordinated with cytoplasmic degradation, and thus this mechanism may predominate during times of more sustained Wnt activation. How these different export mechanisms are calibrated to generate different levels and durations of Wnt signals is currently unclear, but Hendriksen et al. (2005) have provided us with new insights into the regulation of β-catenin nuclear export.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Northwestern University, Chicago, IL 60637, USA.

ABSTRACT
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.

Show MeSH