Studying the mechanism of IAP-mediated signalling.

There is increasing evidence that the ubiquitin conjugation system is intimately linked with the regulation of apoptosis. Since IAPs carry a C-terminal RING-finger domain that provides these molecules with E3 ubiquitin protein ligase activity, we are using IAPs as model system to study how ubiquitin transfer is regulated. Moreover, we are also investigating the consequence of ubiquitin modification of target proteins.

All of the major components of UPS are present in Drosophila, albeit, in comparison with mice and humans, at reduced numbers across each class. Taking E1 (ubiquitinactivating enzyme), E2 (ubiquitin-conjugating enzyme), E3 (ubiquitin-protein ligase) and DUB (deubiquitylating enzyme) representation as a whole, Drosophila harbours 61 and 57% less components than human and mouse, respectively, but 57% more than budding yeast. Therefore Drosophila represents an ideal organism to act as a steppingstone between the extensive findings in the unicellular context of yeast and towards translating those findings into a multicellular context. A reduced complexity helps to bypass redundancy or compensation and, in combination with the power of Drosophila genetics, as well as their accessibility to molecular biology and biochemistry, should facilitate further mechanistic discoveries.