Simona Polo
Simona Polo
affiliation: IFOM-FIRC Institute of Molecular Oncology
research area(s): Cell Biology, Chemical Biology
Course: Molecular Medicine: Molecular Oncology and Computational Biology
University/Istitution: Università di Milano, UNIMI-SEMM
1987 - 1991 Undergraduate degree in Biology, University of Milan, Italy.
1991 - 1995 Ph.D. student, Dipartimento di Genetica e Biologia dei Microorganismi, University of Milan, Italy. Research Advisor: Prof. Gianni Deho'.
1996 - 1999 Postdoctoral Fellow, Unit of Human Virology, Dibit San Raffale Hospital, Milan, Italy. Research Advisor: Prof. Paolo Lusso.
1999 - 2002 Postdoctoral Fellow, European Institute of Oncology, Department of Experimental Oncology, Milan, Italy. Research Advisor: Prof. Paolo Di Fiore.
2002 - 2005 Staff scientist at the European Institute of Oncology (IEO), Milan, Italy.
2005 - pres Group Leader at the IFOM-IEO Campus, Milan, Italy.
2006 - pres Associate Professor, University of Milan, Pathology Department, and European School of Molecular Medicine (SEMM) at IFOM-IEO Campus
2009 EMBO Young Investigator
The activity, localization and fate of a vast number of cellular proteins are regulated through ubiquitination, a process whereby one or more ubiquitin (Ub) monomers or chains are covalently attached to target proteins. Of particular interest in signaling is the ability of the Ub modification to induce de novo protein:protein interactions, through the recognition of ubiquitinated proteins by proteins harboring Ub-binding domains (UBDs), a mechanism that sits at the heart of several signaling cascade. This process is tightly controlled within the cell by endogenous signals, such as DNA damage, and exogenous signals such as growth factor stimulation.
In this latter instance, one of the best-characterized model systems is represented by the epidermal growth Factor (EGF). Upon EGF stimulation a variety of proteins are subject to the Ub modification. These include the EGFR and the components of the downstream endocytic machinery. In the past we contributed to clarify the impact of ubiquitination on receptor internalization, intracellular sorting, and ultimate metabolic fate. Now we wish to draw a complete physical and functional map of the molecular machinery involved in the Ub-based endocytosis and signaling of EGFR. Our idea is to integrate a wide proteomic approach to Ub as a signaling device with high-resolution investigations into how Ub can modulate the function of endocytic proteins.
We recently obtained the EGF-regulated Ubiproteome by two complementary purification strategies coupled to quantitative proteomics. Our results unveil a complex impact of EGF on Ub-based signaling networks, which extends well beyond present knowledge. In addition to endocytic proteins, the EGF-regulated Ubiproteome includes a large number of signaling proteins, ubiquitin ligases and deubiquitinating enzymes, transporters and aminoacid permeases, and proteins involved in translation and transcription. Next, we would like to understand how the signal from activated RTKs is delivered to the ubiquitination machinery and to investigate in details the new effectors found by proteomics.
We are also interested in understanding the mechanism of ubiquitin-chain transfer to the substrate. To investigate the E3 catalysis we are pursuing a biochemical approach coupled to X-ray crystallography studies.

1. Sigismund S, Confalonieri S, Ciliberto A, Polo S, Scita G, and Di Fiore PP. P 2011. Endocytosis: cell logistics shape the eukaryotic cell plan. Physiological Reviews. Invited review, accepted.
2. Maspero E, Mari S, Valentini E, Musacchio A, Fish A, Pasqualato S, Polo S. 2011. Structure of the HECT:Ub complex and its role in ubiquitin chain elongation. EMBO Rep. 12: 342-349.
3. Argenzio E, Bange T, Oldrini B, Bianchi F, Peesari R, Mari S, Di Fiore PP, Mann M, and Polo S. 2011. Proteomic snapshot of the EGF-induced ubiquitin network. Mol Syst Biol. 7:462.
4. Frosi Y, Anastasi S, Ballarò C, Varsano G, Castellani L, Maspero E, Polo S, Alemà S, Segatto O. 2010. A two-tiered mechanism of EGFR inhibition by RALT/MIG6 via kinase suppression and receptor degradation. J Cell Biol. 189:557-71.
5. Lai FP, Szczodrak M, Oelkers JM, Ladwein M, Acconcia F, Benesch S, Auinger S, Faix J, Small JV, Polo S, Stradal TE, Rottner K. 2009. Cortactin promotes migration and platelet-derived growth factor-induced actin reorganization by signaling to Rho-GTPases. Mol Biol Cell. 20:3209-23
6. Acconcia F, Sigismund S, Polo S. 2009. Ubiquitin in trafficking: the network at work. Exp Cell Res. 315:1610-8.
7. Polo, S., and P.P. Di Fiore. 2008. Finding the right partner: SCIENCE or ART? Cell 135:590-592.
8. Sigismund, S., E. Argenzio, D. Tosoni, E. Cavallaro, S. Polo*, and P.P. Di Fiore*. 2008. Clathrin-mediated internalization is essential for sustained EGFR signaling but dispensable for degradation. Dev Cell 15:209-219. *co-corrisponding authors. (76 citations)
9. Woelk, T., S. Sigismund, L. Penengo, and S. Polo. 2007. The ubiquitination code: a signalling problem. Cell Div 2:11.
10. Woelk, T., B. Oldrini, E. Maspero, S. Confalonieri, E. Cavallaro, P.P. Di Fiore, and S. Polo. 2006. Molecular mechanisms of coupled monoubiquitination. Nat Cell Biol 8:1246-1254. (57 citations)
11. Polo, S., and P.P. Di Fiore. 2006. Endocytosis conducts the cell signaling orchestra. Cell 124:897-900.
12. Penengo, L., M. Mapelli, A.G. Murachelli, S. Confalonieri, L. Magri, A. Musacchio, P.P. Di Fiore*, S. Polo*, and T.R. Schneider*. 2006. Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin. Cell 124:1183-1195. *co-corrisponding authors. (83 citations)
13. Sigismund, S., T. Woelk, C. Puri, E. Maspero, C. Tacchetti, P. Transidico, P.P. Di Fiore, and S. Polo. 2005. Clathrin-independent endocytosis of ubiquitinated cargos. Proc Natl Acad Sci U S A 102:2760-2765. (298 citations)
14. Mao, Y., F. Senic-Matuglia, P.P. Di Fiore, S. Polo, M.E. Hodsdon, and P. De Camilli. 2005. Deubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain. Proc Natl Acad Sci U S A 102:12700-12705.
15. Innocenti, M., S. Gerboth, K. Rottner, F.P. Lai, M. Hertzog, T.E. Stradal, E. Frittoli, D. Didry, S. Polo, A. Disanza, S. Benesch, P.P. Di Fiore, M.F. Carlier, and G. Scita. 2005. Abi1 regulates the activity of N-WASP and WAVE in distinct actin-based processes. Nat Cell Biol 7:969-976.
16. Benesch, S., S. Polo, F.P. Lai, K.I. Anderson, T.E. Stradal, J. Wehland, and K. Rottner. 2005. N-WASP deficiency impairs EGF internalization and actin assembly at clathrin-coated pits. J Cell Sci 118:3103-3115.
17. Sigismund, S., S. Polo, and P.P. Di Fiore. 2004. Signaling through monoubiquitination. Curr Top Microbiol Immunol 286:149-185.
18. Polo, S., S. Pece, and P.P. Di Fiore. 2004. Endocytosis and cancer. Curr Opin Cell Biol 16:156-161.
19. Polo, S., S. Confalonieri, A.E. Salcini, and P.P. Di Fiore. 2003. EH and UIM: endocytosis and more. Sci STKE 2003:re17.
20. Haglund, K., S. Sigismund, S. Polo, I. Szymkiewicz, P.P. Di Fiore, and I. Dikic. 2003. Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation. Nat Cell Biol 5:461-466.
21. Di Fiore, P.P., S. Polo, and K. Hofmann. 2003. When ubiquitin meets ubiquitin receptors: a signalling connection. Nat Rev Mol Cell Biol 4:491-497.
22. Chen, H., S. Polo, P.P. Di Fiore, and P.V. De Camilli. 2003. Rapid Ca2+-dependent decrease of protein ubiquitination at synapses. Proc Natl Acad Sci U S A 100:14908-14913.
23. Bianchi, E., S. Denti, R. Catena, G. Rossetti, S. Polo, S. Gasparian, S. Putignano, L. Rogge, and R. Pardi. 2003. Characterization of human constitutive photomorphogenesis protein 1, a RING finger ubiquitin ligase that interacts with Jun transcription factors
24. Poupon, V., S. Polo, M. Vecchi, G. Martin, A. Dautry-Varsat, N. Cerf-Bensussan, P.P. Di Fiore, and A. Benmerah. 2002. Differential nucleocytoplasmic trafficking between the related endocytic proteins Eps15 and Eps15R. J Biol Chem 277:8941-8948.
25. Polo, S., S. Sigismund, M. Faretta, M. Guidi, M.R. Capua, G. Bossi, H. Chen, P. De Camilli, and P.P. Di Fiore. 2002. A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins. Nature 416:451-455. (345 citations)
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