Journal
CELL DEATH & DISEASE
Volume 4, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2013.370
Keywords
RanBP2; Nup358; importin; karyopherin; centrosome
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) Japan
- Asahi Glass Foundation
- Suzuken Memorial Foundation
- Sumitomo Foundation
- Kowa Life Science Foundation
- Mochida Memorial Foundation
- Sagawa Foundation
- Inamori Foundation
- Uehara Memorial Foundation
- Takeda Science Foundation
- Hayashi Memorial Foundation for Women Natural Scientists
- Grants-in-Aid for Scientific Research [23310151, 24121710, 24650611] Funding Source: KAKEN
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Chromosomal missegregation is a common feature of many human tumors. Recent studies have indicated a link between nucleoporin RanBP2/Nup358 and chromosomal segregation during mitosis; however, the molecular details have yet to be fully established. Observed through live cell imaging and flow cytometry, here we show that RNA interference-mediated knockdown of RanBP2 induced G2/M phase arrest, metaphase catastrophe and mitotic cell death. Furthermore, RanBP2 down-modulation disrupted importin/karyopherin beta 1 as well as the expression and localization of the Ran GTPase activating protein 1. We found that N-terminal of RanBP2 interacted with the N-terminal of importin beta 1. Moreover, at least a portion of RanBP2 partially localizes at the centrosome during mitosis. Notably, we also found that GTPase Ran is also involved in the regulation of RanBP2-importin beta 1 interaction. Overall, our results suggest that mitotic arrest and the following cell death were caused by depletion of RanBP2. Our findings point to a crucial role for RanBP2 in proper mitotic progression and faithful chromosomal segregation.
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