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J Biol Chem. 2015 Dec 4;290(49):29375-88. doi: 10.1074/jbc.M115.681908. Epub 2015 Oct 21.

Retinoblastoma-binding Protein 4-regulated Classical Nuclear Transport Is Involved in Cellular Senescence.

Author information

1
From the Graduate School of Medicine and the Laboratories of Nuclear Transport Dynamics and.
2
the Laboratories of Nuclear Transport Dynamics and.
3
Bioinformatics.
4
the Graduate School of Life Science, Hokkaido University, Sapporo, Hokkaido 001-0021, Japan.
5
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.
6
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.

Abstract

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.

KEYWORDS:

IBB; cellular regulation; cellular senescence; importin α; importin β1; nuclear transport; protein-protein interaction; structural model

PMID:
26491019
PMCID:
PMC4705941
DOI:
10.1074/jbc.M115.681908
[Indexed for MEDLINE]
Free PMC Article

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