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

• DOI: 10.1242/jcs.197905
• Publication Date: 2017-06-10T01:02:20Z
• Authors: Eugenia Gilistro; Valeria de Turris; Michela Damizia; Annalisa Verrico; Sara Moroni; Riccardo De Santis; Alessandro Rosa; Patrizia Lavia
• Keywords: Importin

Protein conjugation with small ubiquitin-related modifier (SUMO) is a post-translational modification that modulates protein interactions and localisation. RANBP2 large nucleoporin endowed SUMO E3 ligase SUMO-stabilising activity, implicated in some cancer types. part of larger complex, consisting SUMO-modified RANGAP1, the GTP-hydrolysis activating factor for GTPase RAN. During mitosis, RANBP2-SUMO-RANGAP1 complex localises to mitotic spindle kinetochores after microtubule attachment. Here, we address mechanisms regulate this localisation how they affect kinetochore functions. Using proximity ligation assays, find nuclear transport receptors importin-β CRM1 play essential roles localising away from, or at kinetochores, respectively. newly generated inducible cell lines, show overexpression affects timing opposite ways. Concomitantly, functions are also affected, including accumulation SUMO-conjugated topoisomerase-IIα stability fibres. These results delineate novel mechanism through which govern functional state by regulating timely deposition RANBP2.