Abstract:
FOXO is a family of transcription factor that is involved in many vital cellular processes;
one of its functions is modulating the cellular response to oxidative stress. Heat Shock Proteins
(Hsp) are molecular chaperonins that are upregulated in response to protein denaturation and
aggregation that can result from oxidative stress. The FOXO ortholog in C. elegans and
Drosophila are both capable of inducing expression of Hsp in response to oxidative stress.
Unlike invertebrates, mammals have four FOXO proteins, FOXO1, FOXO3 and FOXO4. I
investigate whether these FOXOs are capable of inducing expression of small and/or large Hsps
in mammalian cells and if FOXO induces Hsp expression in response to oxidative stress. The
treatment of HEK 293T cells with Paraquat, an herbicide that introduces oxidative stress, was
sufficient to increase the expression of Hsps. When FOXO1, FOXO3 or FOXO4 was
overexpressed in 293T cells, there was an increase in expression of both small and large Hsps
examined (Hsp 70A, Hsp 22 and Hsp 27). All of the FOXO proteins caused the induction of at
least two fold in each of the Hsp, however the level of induction differs between FOXOs. This
suggests that perhaps the effect of FOXO induction might vary among Hsps.
