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Importin-β and CRM1 control a RANBP2 spatiotemporal switch essential for mitotic kinetochore function.

Authors
  • Gilistro, Eugenia1
  • de Turris, Valeria2
  • Damizia, Michela1
  • Verrico, Annalisa1
  • Moroni, Sara1
  • De Santis, Riccardo2, 3
  • Rosa, Alessandro2, 3
  • Lavia, Patrizia4
  • 1 CNR National Research Council of Italy, Institute of Molecular Biology and Pathology (IBPM), ℅ Department of Biology and Biotechnology, Sapienza Università di Roma, Via degli Apuli 4, 00185 Rome, Italy. , (Italy)
  • 2 Istituto Italiano di Tecnologia, Center for Life [email protected], Viale Regina Elena 291, 00161 Rome, Italy. , (Italy)
  • 3 Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy. , (Italy)
  • 4 CNR National Research Council of Italy, Institute of Molecular Biology and Pathology (IBPM), ℅ Department of Biology and Biotechnology, Sapienza Università di Roma, Via degli Apuli 4, 00185 Rome, Italy [email protected] , (Italy)
Type
Published Article
Journal
Journal of Cell Science
Publisher
The Company of Biologists
Publication Date
Aug 01, 2017
Volume
130
Issue
15
Pages
2564–2578
Identifiers
DOI: 10.1242/jcs.197905
PMID: 28600321
Source
Medline
Keywords
License
Unknown

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.

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