Chemical and molecular biological approaches to elucidate the biochemical and biological functions of polyubiquitin chains

Description

Modification of proteins by the covalent attachment of ubiquitin plays a fundamental role in the control of many biological processes including cell cycle regulation, transcriptioin, DNA repair, and apoptosis. Substrate proteins are often modified by the attachment of polyubiquitin chains consisting of several ubiquitin moieties linked to each other via isopeptide bond formation. Ubiquitin contains 7 lysine residues and each of these lysines can be used for polyubiquitin chain information. Importantly, it appears that the actual lysine residue of ubiquitin used for ubiquitn-ubiquitin conjugation determines the biochemical/biological function of the respective polyubiquitin chain. For example, K48-linked polyubiquitin chains serve as a signal to target modified proteins for degradation by the proteasome, while K63-linked polyubiquiton chains have been linked to non-proteolytic processes. An attraktive possibility is that the different function(s) of different polyubiquitin chains are mediated by proteins that selectively interact with the respective chain. However, with the exception of proteins interacting with K48-linked polyubiquitin chains, little is known about the identity of such proteins. In the project, a series of chemically defined polyubiquitin chains that differ by the lysine residue used for ubiquitin-ubiquitin conjugation will be synthesized by chemical and biochemicals means. The different chains will be used to generate antibodies and to isolate and characterize proteins that selectively recognize distinct polyubiquitin chains in a linkage-specific manner. Thus, the studies will contribute to the elucidation fo the biochemical and physiological function(s) of different polyubiquitin chains.

Institutions
  • FB Biologie
Funding sources
NameProject no.DescriptionPeriod
Deutsche Forschungsgemeinschaft582/0501.07.2005 – 30.06.2008
Deutsche Forschungsgemeinschaft659/0701.08.2007 – 31.07.2008
Further information
Period: 01.07.2005 – 31.07.2008