Project Title
Comparison of P body Protein Relocalization to Aggresomes Formed in Response to Adenovirus Infections or Chemical Stress
Faculty Mentor(s) Name(s)
Dr. Kasey Karen
Abstract
During an adenovirus infection, the viral protein E4 11k is responsible for relocalizing specific host cell proteins in order to disrupt normal cellular function to support viral replication. E4 11k has been shown to relocalize processing body (p body) proteins to cytoplasmic aggresomes. These aggresomes are regions of misfolded protein storage that are induced when there is cellular stress. The p body protein Ddx6 has been found in E4 11k-induced aggresomes, but it remained in p bodies in cells treated with the chemical stressor cadmium chloride. Ddx6 was also found to bind directly to E4 11k, which suggests that E4 11k may possess a mechanism to relocate Ddx6 during an infection. Ddx6, along with Pat1b and Edc3, are scaffolding proteins involved in p body formation. As scaffolding proteins are involved in many protein-protein interactions, it is likely the mechanism E4 11k uses to relocate other p body proteins is through interaction with one of these proteins. HeLa cells will be treated with cadmium chloride to induce aggresome formation and several p body proteins will be stained, along with gamma tubulin, to indicate which p body proteins are relocalized to aggresomes. We expect at least one p body scaffolding protein to move to aggresomes during this cellular stress.
Comparison of P body Protein Relocalization to Aggresomes Formed in Response to Adenovirus Infections or Chemical Stress
During an adenovirus infection, the viral protein E4 11k is responsible for relocalizing specific host cell proteins in order to disrupt normal cellular function to support viral replication. E4 11k has been shown to relocalize processing body (p body) proteins to cytoplasmic aggresomes. These aggresomes are regions of misfolded protein storage that are induced when there is cellular stress. The p body protein Ddx6 has been found in E4 11k-induced aggresomes, but it remained in p bodies in cells treated with the chemical stressor cadmium chloride. Ddx6 was also found to bind directly to E4 11k, which suggests that E4 11k may possess a mechanism to relocate Ddx6 during an infection. Ddx6, along with Pat1b and Edc3, are scaffolding proteins involved in p body formation. As scaffolding proteins are involved in many protein-protein interactions, it is likely the mechanism E4 11k uses to relocate other p body proteins is through interaction with one of these proteins. HeLa cells will be treated with cadmium chloride to induce aggresome formation and several p body proteins will be stained, along with gamma tubulin, to indicate which p body proteins are relocalized to aggresomes. We expect at least one p body scaffolding protein to move to aggresomes during this cellular stress.