Retinoblastoma-binding Protein 4-regulated Classical Nuclear Transport Is Involved in Cellular Senescence.
Nucleocytoplasmic trafficking is a fundamental cellular process in eukaryotic cells. Here, we demonstrated that retinoblastoma-binding protein 4 (RBBP4) functions as a novel regulatory factor to increase the efficiency of importin α/β-mediated nuclear import. RBBP4 accelerates the release of importin β1 from importin α via competitive binding to the importin β-binding domain of importin α in the presence of RanGTP. Therefore, it facilitates importin α/β-mediated nuclear import. We showed that the importin α/β pathway is down-regulated in replicative senescent cells, concomitant with a decrease in RBBP4 level. Knockdown of RBBP4 caused both suppression of nuclear transport and induction of cellular senescence. This is the first report to identify a factor that competes with importin β1 to bind to importin α, and it demonstrates that the loss of this factor can trigger cellular senescence.
From the Graduate School of Medicine and the Laboratories of Nuclear Transport Dynamics and.
Akira
A
Tsujii
the Laboratories of Nuclear Transport Dynamics and.
Yoichi
Y
Miyamoto
the Laboratories of Nuclear Transport Dynamics and.
Tetsuji
T
Moriyama
Bioinformatics.
Yuko
Y
Tsuchiya
the Graduate School of Life Science, Hokkaido University, Sapporo, Hokkaido 001-0021, Japan.
Chikashi
C
Obuse
Bioinformatics.
Kenji
K
Mizuguchi
the Laboratories of Nuclear Transport Dynamics and Laboratory of Biomedical Innovation, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, moka@nibiohn.go.jp.
Masahiro
M
Oka
Laboratory of Biomedical Innovation, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, and y-yoneda@nibiohn.go.jp.
Yoshihiro
Y
Yoneda
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism; D016922:Cellular Senescence; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D056505:Retinoblastoma-Binding Protein 4 / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D028961:beta Karyopherins / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000378:metabolism
C082637:RBBP4 protein, human; D011994:Recombinant Proteins; D056505:Retinoblastoma-Binding Protein 4; D028961:beta Karyopherins; D005982:Glutathione Transferase; D020931:ran GTP-Binding Protein
IBB; cellular regulation; cellular senescence; importin α; importin β1; nuclear transport; protein-protein interaction; structural model