Presentation Type
Poster
Evaluating the Roles of DBC1 and Aros in the Heat Shock Response
Abstract
The heat shock response (HSR) is a mechanism that serves to repair proteins damaged by stress. Upon heat shock, Heat Shock Factor 1 (HSF1) binds DNA and transcribes the genes for heat shock proteins (HSPs) which serve as molecular chaperones that manage protein damage. Acetylation of HSF1 results in its dissociation from the DNA and attenuation of the HSR. SIRT1 is a deacetylase that prevents the acetylation of HSF1, thus promoting the HSR. Therefore, the regulation of SIRT1 may be useful in designing mechanisms to control the levels of HSPs.
Two modulators of SIRT1 activity include the positive and negative regulators AROS and DBC1, respectively. We investigated the impact that over-expressing AROS and DBC1 have on the HSR. The transcriptional and translational levels of HSP70 throughout a heat shock time course were evaluated via qPCR and Western blotting. While no significant effect on the HSR was observed by Western blot analysis, there was a significant increase in HSP70 mRNA in cells over-expressing AROS and a decrease in cells over-expressing DBC1.
HSP levels are over-expressed during tumorigenesis and protein misfolding is characteristic of Alzheimer’s and Parkinson’s. Therefore, the regulation of SIRT1 may have therapeutic significance in regards to cancer and protein aggregate diseases.
Categories
Natural Sciences
Research Type
Thesis
Mentor Information
Dr. Sandy Westerheide
Evaluating the Roles of DBC1 and Aros in the Heat Shock Response
The heat shock response (HSR) is a mechanism that serves to repair proteins damaged by stress. Upon heat shock, Heat Shock Factor 1 (HSF1) binds DNA and transcribes the genes for heat shock proteins (HSPs) which serve as molecular chaperones that manage protein damage. Acetylation of HSF1 results in its dissociation from the DNA and attenuation of the HSR. SIRT1 is a deacetylase that prevents the acetylation of HSF1, thus promoting the HSR. Therefore, the regulation of SIRT1 may be useful in designing mechanisms to control the levels of HSPs.
Two modulators of SIRT1 activity include the positive and negative regulators AROS and DBC1, respectively. We investigated the impact that over-expressing AROS and DBC1 have on the HSR. The transcriptional and translational levels of HSP70 throughout a heat shock time course were evaluated via qPCR and Western blotting. While no significant effect on the HSR was observed by Western blot analysis, there was a significant increase in HSP70 mRNA in cells over-expressing AROS and a decrease in cells over-expressing DBC1.
HSP levels are over-expressed during tumorigenesis and protein misfolding is characteristic of Alzheimer’s and Parkinson’s. Therefore, the regulation of SIRT1 may have therapeutic significance in regards to cancer and protein aggregate diseases.
