Restoring the Normal Sumoylated Proteins Expression in Alcoholic Liver Disease and Cancer Using a Proteomic Approach In Vivo Model
Post-translational modifications play an important role in regulating protein activity by altering their functions. Sumoylation is a highly dynamic process, which is tightly regulated by a fine balance between conjugating and deconjugating enzyme activities. Sumoylation affects intracellular localizations and their interactions with their binding partners, thereby changing gene expression.
These changes in gene expression in turn affect signaling mechanisms that regulate many cellular functions, such as cell growth, proliferation, apoptosis, DNA repair and cell survival. It is becoming apparent that deregulation in the small ubiquitin-related modifier pathway contributes to oncogenic transformation by affecting sumoylation/desumoylation of many oncoproteins and tumor suppressors. Loss of balance between sumoylation and desumoylation has been reported in a number of studies in a variety of disease types, including cancer. The role of sumoylation in alcoholic liver diseases such as steatosis, steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma is unknown. Given that alcoholic liver disease (ALD) is the major cause of liver disease in Western countries, the goal of research in the Tomasi Lab is to provide highly novel information on the role of sumoylation in the development of ALD.