Ubiquitin and Ub-like interactomes in regulation of cellular functions

• Applicant: Professor Dr. Ivan Dikic
• Subject Area: Biochemistry
• Term: from 2006 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 27748112

Protein ubiquitylation (ubiquitination), the attachment of a small polypeptide ubiquitin (Ub) to protein substrates, is an evolutionary conserved mechanism that controls a wide variety of cellular functions, including proteasomal degradation, intracellular trafficking, DNA repair, gene transcription and virus budding. Our recent discovery of novel Ub-binding domains has indicated how Ub may specifically regulate distinct functions of ubiquitylated targets. There are several Ub-like modifiers, e.g. SUMO, FAT10, ISG15, etc., which trigger various cellular responses. Here we propose to clone small binding domains involved in specific recognition of Ub and Ub-like modifiers by using a large-scale yeast-two-hybrid system coupled with bioinformatics, biochemistry, molecular biology and nuclear magnetic resonance (NMR) spectroscopy work. This will lead to detailed mapping of Ub- and Ubl-specific networks tracing the formation of protein-protein interactomes in cells. The information thus gained will be tested in different cell biological systems to evaluate their physiological and pathophysiological functions. Understanding the specificity of Ub and Ub-like interactomes in vivo will have wide implications for biology and medicine as well as for modern therapeutic approaches to human diseases.

• DFG Programme: Research Grants