Dottoressa di ricerca

ciclo: XXXIII

Titolo della tesi: Nuclear transport factors, nucleoporins and SUMOylation in mitotic cells

Protein conjugation with SUMO (Small Ubiquitin-like MOdifier) peptides, or SUMOylation, modulates protein interactions and localization in many cellular dynamic processes. In particular, growing evidence implicate protein SUMOylation in control of mitosis. Indeed, several factors acting in SUMOylation and deSUMOylation reside at kinetochores. Among them, RANBP2 is a large nucleoporin with SUMO E3 ligase and SUMO stabilizing activity. It is therefore of interest to identify mitotic targets of RANBP2-dependent SUMOylation. Here, by combining Proximity Ligation Assay (PLA) and functional assays, I have identified a key role of RANBP2 in control of the microtubule-regulatory factor NuSAP1 (Nucleolar and spindle-associated protein 1) via temporally and spatially regulated SUMOylation. First, I demonstrated that NuSAP1 is actually SUMOylated in HeLa mitotic cells. Furthermore, I showed that RANBP2 modulates the stability of a NuSAP1 fraction at microtubule plus ends, and needed to stabilize the interactions of chromosomes with the spindle microtubules. To assess directly the effect of NUSAP1 SUMOylation, I mutagenized two putative SUMO consensus sites (K44 and K316, in the DNA-binding and microtubule-binding domain of NuSAP1, respectively). I generated stable inducible cell lines expressing either wild-type NuSAP1 or SUMO mutants. I found that NuSAP1K 316R mutant in the microtubule-binding domain is indeed impaired in microtubule regulatory functions. Together these results indicate that RANBP2-mediated SUMOylation regulates the localization and function of NuSAP1, with implications in the mechanisms regulating chromosome segregation. Loss of this regulation may contribute to originate genetic instability in daughter cells.

Produzione scientifica

11573/1692486 - 2023 - Distinct Mitotic Functions of Nucleolar and Spindle-Associated Protein 1 ({NuSAP}1) Are Controlled by Two Consensus {SUMOylation} Sites
Damizia, Michela; Altieri, Ludovica; Costanzo, Vincenzo; Lavia, Patrizia - 01a Articolo in rivista
rivista: CELLS (Basel: mdpi-Molecular Diversity Preservation International) pp. - - issn: 2073-4409 - wos: WOS:001099604200001 (0) - scopus: 2-s2.0-85176405088 (0)

11573/1669734 - 2022 - Non-transport roles of nuclear import receptors: In need of the right balance
Damizia, Michela; Altieri, Ludovica; Lavia, Patrizia - 01g Articolo di rassegna (Review)
rivista: FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (Lausanne : Frontiers Media S.A., 2013-) pp. - - issn: 2296-634X - wos: WOS:000889873800001 (1) - scopus: 2-s2.0-85142643917 (1)

11573/1600938 - 2021 - Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity
Rossi, Francesca; Beltran Nebot, Manuel; Damizia, Michela; Grelloni, Chiara; Colantoni, Alessio; Setti, Adriano; Di Timoteo, Gaia; Dattilo, Dario; Alvaro, Centrón-Broco; Nicoletti, Carmine; Fanciulli, Maurizio; Lavia, Patrizia; Bozzoni, Irene - 01a Articolo in rivista
rivista: MOLECULAR CELL ([Cambridge, Mass.] : Cell Press, c1997-) pp. 75-89 - issn: 1097-4164 - wos: WOS:000742550300010 (30) - scopus: 2-s2.0-85123392550 (36)

11573/1478280 - 2020 - NUSAP1 (nucleolar and spindle associated protein 1)
Damizia, Michela; Lavia, Patrizia - 02d Voce di Enciclopedia/Dizionario
libro: Atlas of Genetics and Cytogenetics in Oncology and Haematology - ()

11573/1347578 - 2020 - Importin-β/karyopherin-β1 modulates mitotic microtubule function and taxane sensitivity in cancer cells via its nucleoporin-binding region
Verrico, Annalisa; Rovella, Paola; Di Francesco, Laura; Damizia, Michela; Staid, David Sasah; Le Pera, Loredana; Schininà, M Eugenia; Lavia, Patrizia - 01a Articolo in rivista
rivista: ONCOGENE (Macmillan Magazines Limited:Porters South Crinian Street, London N1 9XW United Kingdom:011 44 207 8334000, 011 44 171 8434982, Fax: 011 44 207 812358) pp. - - issn: 0950-9232 - wos: WOS:000507766400015 (3) - scopus: 2-s2.0-85071918983 (3)

11573/1347095 - 2019 - The Mitotic Apparatus and Kinetochores in Microcephaly and Neurodevelopmental Diseases
Degrassi, Francesca; Damizia, Michela; Lavia, Patrizia - 01a Articolo in rivista
rivista: CELLS (Basel: mdpi-Molecular Diversity Preservation International) pp. 49- - issn: 2073-4409 - wos: WOS:000515398200049 (16) - scopus: 2-s2.0-85087624202 (5)

11573/1010898 - 2017 - Importin-beta and CRM1 control a RANBP2 spatiotemporal switch essential for mitotic kinetochore function
Gilistro, Eugenia; De Turris, Valeria; Damizia, Michela; Verrico, Annalisa; Moroni, Sara; De Santis, Riccardo; Rosa, Alessandro; Lavia, Patrizia - 01a Articolo in rivista
rivista: JOURNAL OF CELL SCIENCE (The Company of Biologists Limited:Bidder Building, 140 Cowley Road, Cambridge CB4 0DL United Kingdom:011 44 1223 420482, EMAIL: mandy@thecob.demon.co.uk, INTERNET: http://www.biologists.com, Fax: 011 44 1223 423353) pp. 2564-2578 - issn: 0021-9533 - wos: WOS:000406770700013 (12) - scopus: 2-s2.0-85026638088 (12)

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