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General description: The general interest of my research is to characterize the molecular mechanisms that underlie intracellular signalling events, with particular emphasis on the connection between ubiquitination events and the endocytic processes. In particular, our main interest will involve the study of Rabex-5, a known guanine nucleotide exchange factor for Rab5, in order to define a possible link between RTK activation at the plasma membrane and the downstream signalling events.
Role in RUBICON:
Recent studies in Di Fiore’s group discovered two novel UBDs in Rabex-5. Additionally, Rabex-5 was shown to be subject to mono-ubiquitination itself, as seen for many other ubiquitin-binding proteins. These structural and biochemical characteristics are independent of the GEF activity of Rabex-5 on Rab5, suggesting additional functions of Rabex-5. I intend to unravel i) the role of the UBDs and of the mono-ubiquitination in the regulation of Rabex-5, ii) if Rabex-5 functions as a ubiquitin ligase through its RUZ domain in vitro and in vivo, and eventually to characterize possible substratesto, iii) possible novel functions of Rabex-5 in receptor mediated endocytosis and signalling.
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