Mechanistic study on the interaction between heat shock protein 90 and its chaperone p23
Poster Number
16
Introduction/Abstract
Many cancers overexpress the aryl hydrocarbon receptor (AhR) protein, which is a xenobiotic-sensitive signaling molecule involved in many diseases such as autoimmune diseases, stem cell differentiation, diabetes, and asthma. Currently, we have very limited understanding of the molecular mechanisms explaining how the stable state level of AhR is maintained in a cell. Previously, our lab has shown that reduction of the p23 protein, which is a component of the AhR cytoplasmic complex, causes an increase in degradation of the AhR protein. Exogenous p23 restores this phenotype, clearly showing that p23 is important in controlling AhR protein degradation. It is well established that p23 interacts directly with heat shock protein 90 (Hsp90). We hypothesize that the mechanism of how p23 regulates AhR protein degradation is Hsp90-dependent. This poster focuses on the requirement of p23 to interact with Hsp90.
Purpose
To determine which p23 mutants does not interact with Hsp90.
Method
We generated several p23 mutants via site-directed mutagenesis based on the literature knowledge regarding p23-Hsp90 interaction. The mutant’s ability to bind Hsp90 was assessed through glutathione-s-transferase pull-down assay.
Results
We have been able to determine that certain amino acids that have been coined “essential” for binding Hsp90 still have an affinity to Hsp90 when mutated.
Significance
By better understanding how p23 interacts with Hsp90 and, moreover, how p23 regulates AhR protein degradation, this could help us to rationally design drugs to modulate the AhR protein levels by either increasing or decreasing the AhR protein degradation pathways. These drugs may potentially be used to treat cancers, autoimmune diseases, stem cell differentiation, diabetes, and asthma.
Location
DeRosa University Center, Stockton campus, University of the Pacific
Format
Poster Presentation
Mechanistic study on the interaction between heat shock protein 90 and its chaperone p23
DeRosa University Center, Stockton campus, University of the Pacific
Many cancers overexpress the aryl hydrocarbon receptor (AhR) protein, which is a xenobiotic-sensitive signaling molecule involved in many diseases such as autoimmune diseases, stem cell differentiation, diabetes, and asthma. Currently, we have very limited understanding of the molecular mechanisms explaining how the stable state level of AhR is maintained in a cell. Previously, our lab has shown that reduction of the p23 protein, which is a component of the AhR cytoplasmic complex, causes an increase in degradation of the AhR protein. Exogenous p23 restores this phenotype, clearly showing that p23 is important in controlling AhR protein degradation. It is well established that p23 interacts directly with heat shock protein 90 (Hsp90). We hypothesize that the mechanism of how p23 regulates AhR protein degradation is Hsp90-dependent. This poster focuses on the requirement of p23 to interact with Hsp90.
