Beta-catenin can bind directly to CRM1 independently of adenomatous polyposis coli, which affects its nuclear localization and LEF-1/beta-catenin-dependent gene expression.
Nuclear beta-catenin affects the developmental process and progression of tumors. However, the precise mechanism for the nuclear export of beta-catenin is not completely understood. We found that beta-catenin can bind directly to CRM1 through its central armadillo (ARM) repeats region, independently of the adenomatous polyposis coli (APC) protein. CRM1 overexpression transports nuclear beta-catenin into the cytoplasm and decreases LEF-1/beta-catenin-dependent transcriptional activity, which is also affected by the co-overexpression of E-cadherin. CRM1 competed with E-cadherin and LEF-1 for binding to beta-catenin. beta-catenin could interact directly with APC through its essential sequences between amino acids 342 and 350. The site-directed beta-catenin mutant (NES2(-)), which could interact with CRM1, but not with APC, still retained its ability to export from the nucleus and its transactivational activity. This suggests that CRM1 can function as an efficient nuclear exporter for beta-catenin independently of APC. These results strongly suggest that the CRM1-mediated pathway is involved in the efficient transport of nuclear beta-catenin in the nucleus of cells.
Ki
Hyunkyoung
H
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, 300 Yongbong-dong, Gwangju, South Korea.
Oh
Minsoo
M
Chung
Su Wol
SW
Kim
Kwonseop
K
D021581:Active Transport, Cell Nucleus; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D015820:Cadherins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D005786:Gene Expression Regulation; D028884:Karyopherins / Q000378:metabolism*; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D049790:Nuclear Export Signals; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D051176:beta Catenin / Q000737:chemistry / Q000378:metabolism*; D000097606:Exportin 1 Protein
D025601:Adenomatous Polyposis Coli Protein; D015820:Cadherins; D028884:Karyopherins; D051821:Lymphoid Enhancer-Binding Factor 1; D049790:Nuclear Export Signals; D018160:Receptors, Cytoplasmic and Nuclear; D051176:beta Catenin; D000097606:Exportin 1 Protein