Biogenese des Proteasoms in Saccharomyces cerevisiae

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In eukaryotes, 20S proteasomes are formed from two preassembled precursor complexes that closely resemble half-proteasomes. We have identified a protein, Ump1p, that is present in these complexes, and that is required for proper maturation of 20S proteasomes in S.cerevisiae.We will use a combination of biochemical and genetic approaches to study, in detail, the composition and structure of such precursor complexes, and the nature of interactions between its subunits and Ump1p that lead to its formation. Above that, our prime goal is to understand the processes that control the assembly of 20S proteasome from two such precursors and the formation of active sites through processing of beta-subunits. Several observations indicate that a specific interaction between Ump1p and the propeptide of Pre2p (beta5) triggers the proteasome activation upon its assembly from two precursor complexes. To test this idea we have begun to determine the domains in these two polypeptides whose interactions are underlying this process.Our recent results show that maturation factors related to Ump1p apparently exist in all eukaryotes. A comparison of these relatives has provided important guides to the identification of sequence or structure elements critical to assembly of Ump1p into precursor complexes and/or its function in beta subunit maturation.