|M.Sc Student||Matiuhin Yulia|
|Subject||Mapping of Interactions between Ubiquitin-binding|
Proteins and the 26S Proteasome
|Department||Department of Biology||Supervisor||Professor Michael Glickman|
Degradation of short-lived intracellular proteins is regulated by the ubiquitin -proteasome pathway. The first step of this process is covalent attachment of a polyubiquitin chain to the substrate, which destines it for degradation by the 26 proteasome. The delivery mechanism of tagged substrates to the proteasome is not fully understood. Presumably, there is a series of shuttle proteins that pick up polyubiquitinated substrates in the cell and deliver them to the proteasome. One such shuttle has been claimed to be Rpn10. There is another family of protein including three members - Rad23, Dsk2 and Ddi1 that similarly to Rpn10 can interact both with the proteasome and with the polyubiquitin. These proteins are, however, structurally unrelated to Rpn10. Our work presents novel results regarding functional dissimilarity among these proteins. Our finding is that Rpn10 can specifically bind Dsk2 but not to other ubiquitin-binding proteins under study. The biological importance of the Rpn10-Dsk2 interaction is further investigated. In the absence of Rpn10 the affinity of Dsk2 to the proteasome increases therefore Rpn10 does not serve as a shuttle for Dsk2. We suggest that the two forms of Rpn10 perform distinct cellular functions that are mediated by its two different domains. In summary this work makes important conclusions as to how these shuttles work, how they are regulated, and how are they each unique in some properties.