Date of Award
8-2010
Degree Type
Thesis
Degree Name
MS Biology
Department
Biology
Advisor
Anne M. Pumfery
Committee Member
Allan Blake
Committee Member
Heping Zhou
Committee Member
Carroll Rawn
Keywords
Kaposi's sarcoma, Herpesvirus, Bcl-2 protein, Apoptosis
Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of various diseases, and it encodes a Bcl-2 homolog, KS-Bcl-2. The Bcl-2 family is important in regulating cellular apoptosis. Pro-apoptotic Bcl-2 family members promote apoptosis through mitochondrial pore formation by Bak and Bax, or through BH3 only domain activators and sensitizers. Anti-apoptotic members, such as cellular Bcl-2 prevent apoptosis through interactions with pro-apoptotic proteins, for instance inhibiting pore formation by binding to Bak and/or Bax. Even though, KS-Bcl-2 has been shown to have an anti-apoptotic function like its homolog, it does not bind to either Bak or Bax, and little is known about the mechanism behind KS-Bcl-2's function. A second mitochondrial apoptotic pore is the mPTP, which is made up of ANT and VDAC. Bcl-2 and Bcl-xL have been shown to prevent apoptosis through interactions with these proteins. In order to further investigate the mechanism behind KS-Bcl-2's anti-apoptotic function the localization and binding to the mPTP needed to be determined. KS-Bcl-2 was transfected into Vero cells and then localization was observed under normal and apoptotic conditions. Under normal conditions KS-Bcl-2 localized to the mitochondria, cytoplasm, and nucleus and during apoptosis primarily the mitochondria. Furthermore, to evaluate KS-Bcl-2's interaction with mPTP proteins a OST-pull down assay was performed using isolated GST-KS-Bcl-2 and mitochondrial proteins, and then evaluated for VDAC. It was observed that VDAC and KS-Bcl-2 do interact, and that this interaction could potentially be the mechanism behind KS-Bcl-2's anti-apoptotic function. Further studies are needed to determine the functionality of this interaction.
Recommended Citation
St.Angelo, Erin T., "Localization and Binding Characteristics of Kaposi's Sarcoma-Associated Herpesvirus Bcl-2 Protein in the Prevention of Apoptosis" (2010). Seton Hall University Dissertations and Theses (ETDs). 2456.
https://scholarship.shu.edu/dissertations/2456
