| Cullins (CULs) are a conserved family of proteins that function as E3 ubiquitin ligase components. CUL1 is the most extensively studied and is an important component of the SCF (SKP1, CUL1, F-BOX) complex which is responsible for the degradation of several important substrates. The SCF complex is also part of a larger family of E3s termed CRLs (Cullin-RING Ligases) which are defined by the CUL family member. Our knowledge of CUL1 and the other CULs suggest that their primary role is to act as scaffolds for additional proteins that either aid in substrate or E2 enzyme recruitment. Very little is known about another CUL family member, CUL3. In this thesis we report that the BTB/POZ domain is a CUL3 specific binding module in fission yeast (S. pombe ). The BTB/POZ domain has been conserved through evolution and is found in many proteins. While there only three BTB/POZ domain proteins encoded by the fission yeast genome, there are ∼200 found in humans. We also show that the BTB/POZ domain proteins undergo several different regulatory mechanisms that have been described for other CRL adaptors. For example they can form oligomers and are susceptible to autoubiquitylation. Lastly, we identified a BTB/POZ domain interacting protein, Bre5p which acts as a cofactor for the deubiquitylating protein, Ubp3p. These data suggest an attractive model in which the BTB/POZ domain proteins can influence substrate stability by facilitating either ubiquitylation or deubiquitylation. |
