Nucleo-cytoplasmic shuttling of Axin, a negative regulator of the Wnt-beta-catenin Pathway.
Axin is a negative regulator of the Wnt pathway essential for down-regulation of beta-catenin. Axin has been considered so far as a cytoplasmic protein. Here we show that, although cytoplasmic at steady state, Axin shuttles in fact in and out of the nucleus; Axin accumulates in the nucleus of cells treated with leptomycin B, a specific inhibitor of the CRM1-mediated nuclear export pathway and is efficiently exported from Xenopus oocyte nuclei in a RanGTP- and CRM1-dependent manner. We have characterized the sequence requirement for export and identified two export domains, which do not contain classical nuclear export consensus sequences, and we show that Axin binds directly to the export factor CRM1 in the presence of RanGTP.
Wiechens
Nicola
N
Max-Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen, Germany.
Heinle
Karolin
K
Englmeier
Ludwig
L
Schohl
Anne
A
Fagotto
François
F
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D060466:Axin Protein; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015536:Down-Regulation; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins / Q000378:metabolism*; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D051153:Wnt Proteins; D014981:Xenopus; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D020931:ran GTP-Binding Protein / Q000378:metabolism; D000097606:Exportin 1 Protein
D000903:Antibiotics, Antineoplastic; D060466:Axin Protein; D003598:Cytoskeletal Proteins; D005231:Fatty Acids, Unsaturated; D028884:Karyopherins; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein; C495266:CTNNB1 protein, Xenopus; C495270:CTNNB1 protein, human; C555454:axin1 protein, Xenopus; C038753:leptomycin B