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PMID:23577172

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Citation

Goto, T, Sato, A, Shimizu, M, Adachi, S, Satoh, K, Iemura, S, Natsume, T and Shibuya, H (2013) IQGAP1 Functions as a Modulator of Dishevelled Nuclear Localization in Wnt Signaling. PLoS ONE 8:e60865

Abstract

Dishevelled (DVL) is a central factor in the Wnt signaling pathway, which is highly conserved among various organisms. DVL plays important roles in transcriptional activation in the nucleus, but the molecular mechanisms underlying their nuclear localization remain unclear. In the present study, we identified IQGAP1 as a regulator of DVL function. In Xenopus embryos, depletion of IQGAP1 reduced Wnt-induced nuclear accumulation of DVL, and expression of Wnt target genes during early embryogenesis. The domains in DVL and IQGAP1 that mediated their interaction are also required for their nuclear localization. Endogenous expression of Wnt target genes was reduced by depletion of IQGAP1 during early embryogenesis, but notably not by depletion of other IQGAP family genes. Moreover, expression of Wnt target genes caused by depletion of endogenous IQGAP1 could be rescued by expression of wild-type IQGAP1, but not IQGAP1 deleting DVL binding region. These results provide the first evidence that IQGAP1 functions as a modulator in the canonical Wnt signaling pathway.

Links

PubMed Online version:10.1371/journal.pone.0060865

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

XENTR:F6WBH7

involved_in

GO:0006606: protein import into nucleus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

XENTR:F6WBH7

GO:0060070: canonical Wnt receptor signaling pathway

ECO:0000315:

P

The results presented in Fig. 4 (A-H) suggest “that xIQGAP1 is necessary for Wnt-related early embryogenesis” and functions as an intermediate molecule in the pathway. Additionally, the results in Fig 5 also support that binding between xDVL2 and xIQGAP1 plays an important role in canonical Wnt signaling.

complete
CACAO 7906


See also

References

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