Objective "The principal objective of our broad, translational research is to determine structural attributes and to develop small-molecule compounds for new, emerging, cancer-related protein-protein interactions in the ubiquitin-proteasome system (UPS) and ubiquitin-like protein (UBL) conjugation pathways. We use nuclear magnetic resonance (NMR) and X-ray crystallography techniques to structurally characterize protein-protein interactions (PPI) and to develop small-molecule inhibitors for these PPIs. The UPS and UBL proteins studied by us are: the oncogenic E3 ligase Mdm2, which regulates levels of p53, the deubiquitinating enzyme (DUB) USP2a, and the UBL protein Hub1, which has been recently shown to control alternative splicing by non-covalent binding to the Snu66 spliceosomal protein. The E3 ligases and DUBs are considered to be the most important components of the ubiquitin conjugation system; this is because they directly bind to their target proteins and thus control substrate specificity. Hub1 connects the UBL pathway to the regulations of splice site usage and alternative splicing. Malfunctions in alternative splicing patterns are known to cause, among others, premature aging and cancer. The tumour suppressor p53 protein, ""the guardian of the genome"", has an overarching role in protecting the organism from cancer. In order to escape the safeguard system mediated by p53, nearly all human cancers have compromised the effectiveness of the p53 pathway. The restoration of the impaired function of the single gene, p53, by disrupting the Mdm2- p53/Mdmx-p53 interactions, offers a fundamentally new avenue for anticancer therapy across a broad spectrum of cancers." Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesearth and related environmental sciencesgeologymineralogycrystallographymedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2011-CIG - Marie-Curie Action: "Career Integration Grants" Call for proposal FP7-PEOPLE-2011-CIG See other projects for this call Funding Scheme MC-CIG - Support for training and career development of researcher (CIG) Coordinator Jagiellonian University in Krakow Address Ul. golebia 24 31007 Krakow Poland See on map Region Makroregion centralny Łódzkie Miasto Łódź Activity type Higher or Secondary Education Establishments Administrative Contact Barbara Rys (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data
