Functional analysis of cullin-based ubiquitin ligase and a novel UBC domain-containing protein

Lai Xu

This thesis is composed of two major areas of study: the first study describes yeast two hybrid screen and biochemical approaches which were performed to identify interaction partners for C. elegans CUL-3; the second study focuses on the functional analysis of a novel ubiquitin conjugating (UBC) domain-containing protein FTS (Fused Toes). In the first study, a large family of proteins harboring a conserved BTB domain was identified to partner with Cul3. The BTB domain adopts a structure similar to the Cul1 interacting domain of Skp1. Most of the identified BTB domain proteins also contain an additional potential protein-protein interaction domain, such as MATH domain. We hypothesized based on analogy with the SCF complex, that BTB proteins function as substrate specific adaptors of the Cul3 Ub ligase. Mel-26, an essential MATH-BTB protein was one of the BTB proteins identified from...