Reactome: A Curated Pathway Database

XPO1 binds the beta-catenin:CBY complex

Stable Identifier
R-HSA-3769391
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

CBY1 contains both NLS and NES sequences and continuously shuttles between the cytoplasm and the nucleus. Treatment of cells with leptomycin B (LMB), an inhibitor of XPO1-mediated nuclear export, results in nuclear accumulation of both CBY1 and 14-3-3/YWHAZ proteins (Li et al, 2008; Li et al, 2010). Consistent with this, CBY1 binds to XPO1 in an NES-dependent manner. 14-3-3/YWHAZ enhances the CBY1-XPO1 interaction, possibly by inducing a conformational change that exposes the adjacent NES sequence. Binding of 14-3-3/YWHAZ also inhibits the interaction of CBY1 with alpha-importin, additionally favouring its cytoplasmic localization. CBY1 NES mutants that are incapable of nuclear export show reduced ability to repress a beta-catenin-dependent reporter, and knockdown of endogenous CBY1 causes an accumulation of beta-catenin in the nucleus. These data support a role for CBY1 in the nuclear export of beta-catenin (Li et al, 2010). Despite growing evidence for a role for CBY1 in regulating WNT signaling, a formal requirement for CBY1 in vivo is still lacking.

Literature References
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Orthologous Events