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Tsujii A.,Osaka University | Tsujii A.,Laboratories of Nuclear Transport Dynamics | Miyamoto Y.,Laboratories of Nuclear Transport Dynamics | Moriyama T.,Laboratories of Nuclear Transport Dynamics | And 8 more authors.
Journal of Biological Chemistry | Year: 2015

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 importinα/β-mediated nuclear import. RBBP4 accelerates the release of importin beta;1 from importin α via competitive binding to the importin β-binding domain of importin α in the presence of RanGTP. Therefore, it facilitates importinα/β-mediated nuclear import. Weshowed that the importinα/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 importinβ1 to bind to importinα, and it demonstrates that the loss of this factor can trigger cellular senescence. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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