RanBP3 enhances nuclear export of active β -catenin independently of CRM1
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RanBP3 enhances nuclear ex port of active β-catenin independe ntly of CRM1 Hendriksen et al., JCB(2005)
description
RanBP3 enhances nuclear export of active β -catenin independently of CRM1. Hendriksen et al., JCB(2005). Scheme of canonical Wnt signaling. Nusse et al., JBC , 2006. The Ran cycle. Fahrenkrog and Aebi et al., Nat Rev Mol Cell Biol , 2003. - PowerPoint PPT Presentation
Transcript of RanBP3 enhances nuclear export of active β -catenin independently of CRM1
RanBP3 enhances nuclear export ofactive β-catenin independently of CR
M1
Hendriksen et al., JCB(2005)
Scheme of canonical Wnt signaling
Nusse et al., JBC, 2006
The Ran cycle
Fahrenkrog and Aebi et al., Nat Rev Mol Cell Biol , 2003
Import and export cycle mediated by importin and exportin
Kuersten et al., Trends cell bio, 2001
What is β-catenin?
• A key molecule which mediates cellular activities in the Wnt signaling pathway
• It was first identified as a component of the cell–cell adhesion complex
• It doesn’t have NLS and NES
N-terminus C-terminus
Putative phosphorylation
site(s), mutated in tumors
Ubiquitination sites
α-cateninAPC TCF/LEF-1 E-cadherin
ARM repeat
Nuclear-cytoplasmic shuttling of β-catenin
Fagotto et al., EMBO, 2002
Identification of RanBP3 as an interaction partner of β-catenin
p80
p90
Expression of RanBP3 inhibits β-catenin /TCF–mediated transcriptional activation
Expression of RanBP3 inhibits β-catenin /TCF–mediated transcriptional activation
Reduction of RanBP3 by RNAi results in Increasedβ-catenin / TCF–mediated transcription activation.
RanBP3 antagonizes Wnt/β-catenin transactivationin APC mutated colon carcinoma cells.
Depletion of RanBP3 results in nuclearaccumulation of active β-catenin
RanBP3 induces specific depletionof endogenous nuclear active β-catenin.
RanBP3 enhances nuclear export ofactive β-catenin independently of CRM1.
RanBP3 enhances nuclear export ofactive β-catenin independently of CRM1.
RanBP3 rescues β-catenin–induceddouble axis formation in X. laevis embryos.
RanBP3 rescues β-catenin–induceddouble axis formation in X. laevis embryos.
Loss of RanBP3 by RNAi results in a nakedcuticle phenotype in D. melanogaster.
Loss of RanBP3 by RNAi results in a nakedcuticle phenotype in D. melanogaster.
conclusion
summary
• RanBP3 is a novel inhibitor of Wnt signaling that acts on β-catenin directly by enhancing nuclear export of its active form.
• Expression of RanBP3 represses Wnt signaling both in vitro and in Xenopus embryonic Wnt signaling.
• Inhibition of RanBP3 by RNAi causes overactivation of Wnt signaling in tissue culture cell and Drosophila embryo.
Three pathway of export β-catenin
1. Interact directly with nuclear pore complex (Fagotto et al., Curr. Biol, 2001)
2. Exit via the CRM1 pathway it uses binding APC (Rosin-Arbesfeld et at., Nature, 2000)
3. RanBP3 enhance β-catenin export CRM1 and APC independently (In this paper)
Nuclear export of β-catenin
Gottardi et al., JCB, 2005
