Project: Research project

Project Details


The posttranslational attachment of ubiquitin to proteins is used in
eukaryotes to target a broad range of proteins for selective degradation.
Selective removal of proteins is required for a number of cellular
processes and a requirement for ubiquitin has been shown for processes
ranging from the determination of cell fate in division, differentiation,
oncogenesis and senescence to more specific processes such as DNA repair,
inflammatory response, signal transduction and the removal of abnormal
proteins. Many of these processes are also under intense investigation
because of their relevance in human diseases. Oncogenesis and the
inflammatory responses are two examples.

The specificity of protein ubiquitination is conferred by a family of
related proteins known as ubiquitin conjugating-enzymes (Ubc). Members in
this family interact with a distinct set of substrate-binding proteins
(also known as E3), and it is these cascades of interaction between Ubc and
E3 proteins that enable the pathway to target a broad range of proteins for

Ubc proteins all share a common conserved domain of approximately 150-170
amino acid residues. The Class I enzymes are the smallest and are
comprised entirely of this domain. This conserved domain in larger,
multifunctional Ubc's can also function autonomously. Thus, there must be
unique structural features embedded in the conserved domain of an
individual Ubc protein that enable each enzyme to interact specifically
with its own set of E3 proteins. Analyses of Ubc sequences and the three
known crystal structures of Class I enzymes have led us to formulate a
general model that predicts how similarity and differences in Ubc's are
manifested structurally. Our long term goal is to determine how specific
regions in Ubc proteins are utilized for its function. The specific aims
for this research period is 1) to analyze the effect of mutations on the
function of selected Ubc's in the yeast S. cerevisiae, with the intention
of defining those regions that are responsible for Ubc interaction with E3,
2)to initiate studies toward determining the crystal structure of a Ubc4-E3
complex; 3) to define E3 proteins that function in the Ubc7-dependent
Effective start/end date3/13/964/30/01


  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences


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