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

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 ?/?-mediated nuclear import. RBBP4 accelerates the release of importin ?1 from importin ? via competitive binding to the importin ?-binding domain of importin ? in the presence of RanGTP. Therefore, it facilitates importin ?/?-mediated nuclear import. We showed that the importin ?/? 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 ?1 to bind to importin ?, and it demonstrates that the loss of this factor can trigger cellular senescence.

SUBMITTER: Tsujii A 

PROVIDER: S-EPMC4705941 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature