Cell Cycle and Cancer - PhD and honours Projects - Regulation of cell cycle progression in human cancer
Regulation of cell cycle progression in human cancer
Project Type
PhD
Summary
The ubiquitination pathway involves the covalent binding of the ubiquitin polypeptide to substrate proteins resulting in their recognition and proteolytic degradation by the proteasome. This pathway is involved in all aspects of eukaryotic biology and accounts for 80% of cellular protein turnover. The recent approval of the proteasome inhibitor bortezomib for the treatment of advanced multiple myeloma indicates that targeting the ubquitin/proteasome pathway offers new avenues for cancer therapy. Since the proteasome is non-specific and degrades most polyubiquitylated proteins, the development of drugs against specific lesions in the ubiquitin/proteasome pathway is important for increasing specificity and thus attaining better therapeutic outcomes for more effective cancer treatment. Ubiquitin-conjugating enzymes (UBCs) and ubiquitin-ligases (E3s) are pivotal enzymes in the ubiquitylation pathway. Recent studies demonstrating increased expression of UBC3 and UBCh10 in human tumours, implicate a role for these molecules in human cancer development. Therefore, increased understanding of the molecular mechanisms of UBC and E3 action is pivotal towards evaluating the potential of these molecules as therapeutic drug targets. Our laboratory has unveiled important regions in UBCs and E3s which are critical for the catalytic activity and cell cycle functions of these enzymes. The aim of this research is to completely characterise the importance of these regions for UBC and E3 function at a molecular level and in cell cycle progression. These sites may represent new drug targets to modulate UBCs and E3s for cancer treatment.
Supervisor: Dr Boris Sarcevic