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.
Mesh Terms:
Active Transport, Cell Nucleus, Amino Acid Sequence, Cell Aging, Cell Nucleus, Crystallography, X-Ray, Cytoplasm, Fibroblasts, Glutathione Transferase, HEK293 Cells, HeLa Cells, Humans, Molecular Sequence Data, Protein Binding, Protein Conformation, Recombinant Proteins, Retinoblastoma-Binding Protein 4, Sequence Homology, Amino Acid, beta Karyopherins, ran GTP-Binding Protein
Active Transport, Cell Nucleus, Amino Acid Sequence, Cell Aging, Cell Nucleus, Crystallography, X-Ray, Cytoplasm, Fibroblasts, Glutathione Transferase, HEK293 Cells, HeLa Cells, Humans, Molecular Sequence Data, Protein Binding, Protein Conformation, Recombinant Proteins, Retinoblastoma-Binding Protein 4, Sequence Homology, Amino Acid, beta Karyopherins, ran GTP-Binding Protein
J. Biol. Chem.
Date: Dec. 04, 2015
PubMed ID: 26491019
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