Structural characterization of interaction of K11 and K63 mixed-linkage polyubiquitin chains with the tUIMs of epsin1

Ubiquitylation or covalent attachment of ubiquitin (Ub) to a variety of substrate proteins in cells is a versatile post-translational modification involved in the regulation of numerous cellular processes. The distinct messages that polyubiquitylation encodes are attributed to the multitude of conformations possible through attachment of ubiquitin monomers within a polyubiquitin chain via a specific lysine residue. Thus the hypothesis is that linkage defines polyubiquitin conformation which in turn determines specific recognition by cellular receptors. Ubiquitylation of membrane surface receptor proteins plays a very important role in regulating receptor-mediated endocytosis as well as endosomal sorting for lysosomal degradation. Epsin1 is an endocytic adaptor protein with three tandem UIMs (Ubiquitin Interacting Motifs) which are responsible for the highly specific interaction between epsin and ubiquitylated receptors. Epsin1 is also an oncogenic protein and its expression is upregulated in some types of cancer. Recently it has been shown that novel K11 and K63 mixed-linkage polyubiquitin chains serve as internalization signal for MHC I (Major Histocompatibility Complex I) molecule through their association with the tUIMs of epsin1. However the molecular mode of action and structural details of the interaction between polyubiquitin chains on receptors and tUIMs of epsin1 is yet to be determined. This information is crucial for the development of anticancer therapeutics targeting epsin1. The molecular basis for the linkage-specific recognition of K11 and K63 mixed-linkage polyubiquitin chains by the tandem UIMs of the endocytic adaptor protein epsin1 is investigated using a combination of NMR methods.

CHASING THE SINGERS: THE TRANSITION OF LONG-SONG (URTYN DUU) IN POST-SOCIALIST MONGOLIA

Long-song (Urtyn duu) is a prominent Mongolian traditional folk song genre that survived throughout the socialist period (1921-1990) and throughout the political transformation of Mongolia from socialism to democratic capitalism after the Soviet Union was dismantled and terminated its aid to Mongolia in 1990. This dissertation, based on research conducted from 2006 to 2010, presents and investigates the traces of singers' stories and memories of their lives, songs, and singing, through the lens of the discourse on change and continuity in, and as, folk tradition. During the socialist period, this genre was first considered backward, and was then subtly transformed into an urban national style, with the formation of a boundary between professionalism and amateurism among long-song singers and with selective performance of certain songs and styles. This boundary was associated with politics and ideology and might be thought to have ended when the society entered its post-socialist period. However, the long-song genre continued to play a political role, with different kinds of political meaning one the one hand and only slight musical modification on the other. It was now used to present a more nostalgic and authentic new Mongolian identity in the post-socialist free market. Through my investigation, I argue that the historical transition of Mongolia encompassed not merely political or economic shifts, but also a deeper transformation that resulted in new cultural forms. Long-song provides a good case study of the complicated process of this cultural change.