Bioinformatic approaches to the discovery of apoptotic proteins

The core of this research project revolves around the development of knowledge and expertise in the field of sequence homology identification techniques, as applied towards the discovery of Bcl2 family members. The use of such methods resulted in the uncovering of a Bcl2 Homology 3 (BH3) domain in a ubiquitin ligase enzyme known as upstream regulatory binding protein 1 (UreB1). A complete biochemical analysis unequivocally demonstrated binding of the UreB1 BH3 domain to MCL-1, an antiapoptotic member of the Bcl2 protein family. Furthermore, the discovery of a BH3 domain in UreB1 may provide a link in the established involvement of the ubiquitin pathway in the degradation of Mcl1 following certain apoptotic stimuli. In addition, using an independent domain modelling strategy, we describe the development of BISA, a web-accessible software package for sequence homology detection