Gary F. Merrill
Professor
541-737-3119
Links
Education
Ph.D. 1977, Syracuse University
Research
Several
important transcription factors and signal transduction proteins are
redox sensitive. These proteins often contain cysteine residues that
are oxidized by reactive oxygen species and restored to the reduced
state by thioredoxin. Thioredoxin is a redox active protein which,
together with thioredoxin reductase, is able to transfer reducing
equivalents from NADPH to oxidized protein cystinyl groups. Thioredoxin
is required for proper functioning of several regulatory pathways. For
example, the p53 tumor supressor protein requires reduced thioredoxin
to efficiently stimulate target gene transcription. Similarly, protein
tyrosine phosphatases, which antagonize the activity of tyrosine
kinases, contain oxidation-prone cysteines that are maintained in a
reduced state by thioredoxin. Our laboratory uses biochemical and
genetic approaches to study the role of thioredoxin in redox control
mechanisms. Biochemically, we have developed electrophoretic methods
for measuring the redox state of proteins in vivo, and are
using these methods to determine the basis for and consequences of
oxidation events that occur during growth factor signaling and
oxidative stress. Genetically, we use budding yeast, an organism where
genes can easily be deleted or replaced, to study the effect of
modifying redox control proteins on transcription factor activity and
cell signaling. We are also using knock-out mice to test whether the
functional relationships we have discovered in the yeast system hold
true for mammalian cells.