Redox-dependent Regulation of the Structure and Function of HSF1 in Mammalian Cells

It is well known that the structure and function of proteins and consequently the activity of cells can be regulated by reversible and covalent modification of specific amino acid residues in proteins, and that post-translational modification reactions, such as phosphorylation, provide important biological switches in cells. The goal of Dr. Liu's research project is to establish the posttranslational, oxidation- and reduction- (redox) dependent thiol-disulfide exchange of cysteine-SH as a cellular mechanism regulating the structure and function of heat shock factor 1 (HSF1), an important and ubiquitous transcription factor that responds to stress. Specifically, Dr. Liu and her research team will evaluate if oxidation and covalent crosslinking of cysteines may: (a) provide a mechanism to restrain the inadvertent activation of HSF1 in cells grown under a normal, unstressed condition, or (b) represent a pathophysiological manifestation of oxidative stress that limits the activation of HSF1 and induction of the cellular stress response as Dr. Liu and her colleagues have previously observed in a number of aging cells, tissues, organs, and animals. The successful completion of this research will provide useful information on the relationship of redox-dependent protein modification, transcription factor regulation, and the molecular basis of transcription factor dysfunction under a variety of physiological and pathophysiological conditions. It is anticipated that this research will contribute to the emerging concept that redox-dependent modification of proteins can provide a versatile epigenetic mechanism by which cells regulate important biological processes. The active participation and involvement of undergraduate and graduate students in this research will help to accomplish an important goal of research universities, namely the teaching and training of future research scientists.