Grant: Project Grant

Protein degradation constitutes a major cellular function that is responsible for maintenance of the normal cellular physiology by breaking down proteins. The ubiquitin-proteasome system is one of the major mechanism responsible for protein degradation within cells. The regulation of protein stability by this pathway is critical in the molecular basis of carcinogenesis, as it is involved in the regulation of cell growth and preventing abnormal accumulation of proteins. Additionally, ubiquitin modification of target proteins signals many cellular processes other than proteolysis that are also important for the development of cancer. Deregulation of ubiquitin ligases, which are proteins involved in many biological processes including protein degradation, results in uncontrolled proliferation, genomic instability and cancer. Attempts to develop general protein degradation inhibitors for cancer therapy have been questioned because it is highly toxic, and could results in long-term effects from the accumulation of misfolded proteins that is the hallmark of neurodegenerative diseases. Thus, there is great interests in identifying specific proteins involved in this process that could be targeted instead. We identified UBBP4, a gene encoding novel ubiquitins that could be involved in such specific ubiquitination of proteins. The main goal of studying ubiquitin and ubiquitin ligases is to develop drugs that specifically target these enzymes. Thus, it is crucial to identify the substrates of these ubiquitin ligases and understand their cellular functions. We will be using different innovative approaches to identify the proteins modified by UBBP4, as well as functional role for this new modification. The results obtained from the experiments proposed in this application will allow us to better understand the molecular mechanisms regulated by ubiquitin.