Research ???Area
Department of Experimental Oncology
Viral Control of Cellular Pathways and Biology of Tumorigenesis Susanna CHIOCCA, PhD Director
STAFF Post-doctoral Fellows: Simona Citro, PhD, Domenico Mattoscio, Ph.D, Archana Varadaraj, Ph.D PhD Students: Sara Loponte, Chiara Segré Folsatec Ph.D. student: Paolo Maugeri Technician: Claudia Miccolo Undergraduate Student: Laura Meloni
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IEO — Scientific Report 2011 — Ongoing research 2012
Activities 2011.
Viruses reprogram or convert hosts’ metabolic and replication functions in order to obtain a cellular environment more favorable for viral propagation. We have been studying how viral proteins interfere with the regulation of the SUMO (Small Ubiquitin-related Modifier) pathway, a post-translational modification system enzymatically analogous but functionally diverse from the classical ubiquitin system (Ub). As a model system we have been using a peculiar adenoviral protein called Gam1 and demonstrated indeed how a viral protein can degrade the unique SUMO E1 enzyme by hijacking endogenous cellular components of ubiquitin E3 ligases. Protein post-translational modification by ubiquitin and SUMO regulate pathways that contribute to numerous biological processes. An ongoing research theme in our lab is to understand the cross-talk between the Ub and the SUMO pathways. We have also shown that Histone Deacetylase 1 (HDAC1) is post-translationally modified by SUMO. Mammalian histone deacetylases (HDACs) are composed of ubiquitously expressed class I, tissue specific class II, and NAD-dependent class III enzymes. Human HDACs are targets for cancer therapy. In fact, therapeutic efforts with HDAC inhibitors for the treatment of cancer are being pursued and the role of individual HDACs in tumorigenesis is starting to emerge. HDAC1 can also be phosphorylated, ubiquitinated and acetylated. Therefore, this project is based upon our findings that different interdependent modifications might modulate the biological function of HDAC1. Our laboratory is therefore pursuing two major projects: A. The biology of HDAC1 (and HDAC2) and how its post-translational modifications cross-talk and control its activity, also in light of its potential significance as a target for cancer therapy. B. The regulation of the SUMO pathway, its cross-talk to the ubiquitin pathway using the viral protein Gam1 as
a model system. We are also assessing whether other oncogenic viruses exploit the SUMO pathway. Pubblications Regulating the regulators: the post-translational code of class I HDAC1 and HDAC2. Segré CV, Chiocca S. J Biomed Biotechnol. 2011;2011:690848. Epub 2010 Dec 9. Review. PMID: 21197454 [PubMed - indexed for MEDLINE] Free PMC Article A phosphorylation switch regulates the transcriptional activation of cell cycle regulator p21 by histone
deacetylase inhibitors. Simboeck E, Sawicka A, Zupkovitz G, Senese S, Winter S, Dequiedt F, Ogris E, Di Croce L, Chiocca S, Seiser C. J Biol Chem. 2010 Dec 24;285(52):41062-73. Epub 2010 Oct 14. PMID: 20952396 [PubMed - indexed for MEDLINE] Free PMC Article Listeria monocytogenes: a bacterial pathogen to hit on the SUMO pathway. Citro S, Chiocca S. Cell Res. 2010 Jul;20(7):738-40. Epub 2010 Jun 8. PMID: 20531377 Inhibition of the SUMO pathway by Gam1. Pozzebon M, Segré CV, Chiocca S. Methods Mol Biol. 2009;497:285301. Review.
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