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PMID:16968744

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Citation

Wang, Y, Kakinuma, N, Zhu, Y and Kiyama, R (2006) Nucleo-cytoplasmic shuttling of human Kank protein accompanies intracellular translocation of beta-catenin. J. Cell. Sci. 119:4002-10

Abstract

The human Kank protein has a role in controlling the formation of the cytoskeleton by regulating actin polymerization. Besides the cytoplasmic localization as reported before, we observed the nuclear localization of Kank in OS-RC-2 cells. To uncover the mechanism behind this phenomenon, we focused on the nuclear localization signal (NLS) and the nuclear export signal (NES). We found one NLS (NLS1) and two NESs (NES1 and NES2) in the N-terminal region of Kank-L that were absent in Kank-S, and another NLS (NLS2) and NES (NES3) in the common region. These signals were active as mutations introduced into them abolished the nuclear import (for NLS1 and NLS2) or the nuclear export (for NES1 to NES3) of Kank. The localization of Kank in the cells before and after treatment with leptomycin B suggested that the transportation of Kank from the nucleus to the cytoplasm was mediated by a CRM1-dependent mechanism. TOPFLASH reporter assays revealed a positive relationship between the nuclear import of Kank and the activation of beta-catenin-dependent transcription. Kank can bind to beta-catenin and regulate the subcellular distribution of beta-catenin. Based on the findings shown here, we propose that Kank has multiple functions in the cells and plays different roles in the cytoplasm and the nucleus.

Links

PubMed Online version:10.1242/jcs.03169

Keywords

Active Transport, Cell Nucleus/drug effects; Active Transport, Cell Nucleus/physiology; Animals; Cells, Cultured; Fatty Acids, Unsaturated/pharmacology; Humans; Mice; NIH 3T3 Cells; Nuclear Localization Signals/chemistry; Protein Sorting Signals; Protein Transport/physiology; Tissue Distribution/drug effects; Transcription, Genetic; Tumor Suppressor Proteins/chemistry; Tumor Suppressor Proteins/metabolism; beta Catenin/metabolism

Significance

Annotations

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

HUMAN:CTNB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q14678

F

Seeded From UniProt

complete

HUMAN:KANK1

enables

GO:0008013: beta-catenin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:KANK1

involved_in

GO:0030177: positive regulation of Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:KANK1

involved_in

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:KANK1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35222

F

Seeded From UniProt

complete

HUMAN:KANK1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:KANK1

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:KI21A

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:KI21A

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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