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Importin-β and CRM1 control a RANBP2 spatiotemporal switch essential for mitotic kinetochore function.
- Source :
-
Journal of cell science [J Cell Sci] 2017 Aug 01; Vol. 130 (15), pp. 2564-2578. Date of Electronic Publication: 2017 Jun 09. - Publication Year :
- 2017
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Abstract
- Protein conjugation with small ubiquitin-related modifier (SUMO) is a post-translational modification that modulates protein interactions and localisation. RANBP2 is a large nucleoporin endowed with SUMO E3 ligase and SUMO-stabilising activity, and is implicated in some cancer types. RANBP2 is part of a larger complex, consisting of SUMO-modified RANGAP1, the GTP-hydrolysis activating factor for the GTPase RAN. During mitosis, the RANBP2-SUMO-RANGAP1 complex localises to the mitotic spindle and to kinetochores after microtubule attachment. Here, we address the mechanisms that regulate this localisation and how they affect kinetochore functions. Using proximity ligation assays, we find that nuclear transport receptors importin-β and CRM1 play essential roles in localising the RANBP2-SUMO-RANGAP1 complex away from, or at kinetochores, respectively. Using newly generated inducible cell lines, we show that overexpression of nuclear transport receptors affects the timing of RANBP2 localisation in opposite ways. Concomitantly, kinetochore functions are also affected, including the accumulation of SUMO-conjugated topoisomerase-IIα and stability of kinetochore fibres. These results delineate a novel mechanism through which nuclear transport receptors govern the functional state of kinetochores by regulating the timely deposition of RANBP2.<br />Competing Interests: Competing interestsThe authors declare no competing or financial interests.<br /> (© 2017. Published by The Company of Biologists Ltd.)
- Subjects :
- GTPase-Activating Proteins genetics
GTPase-Activating Proteins metabolism
HeLa Cells
Humans
Karyopherins genetics
Molecular Chaperones genetics
Nuclear Pore Complex Proteins genetics
Receptors, Cytoplasmic and Nuclear genetics
SUMO-1 Protein genetics
SUMO-1 Protein metabolism
beta Karyopherins genetics
Exportin 1 Protein
Karyopherins metabolism
Kinetochores metabolism
Molecular Chaperones metabolism
Nuclear Pore Complex Proteins metabolism
Receptors, Cytoplasmic and Nuclear metabolism
beta Karyopherins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9137
- Volume :
- 130
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Journal of cell science
- Publication Type :
- Academic Journal
- Accession number :
- 28600321
- Full Text :
- https://doi.org/10.1242/jcs.197905