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Kaposi's Sarcoma‐Associated Herpesvirus (KSHV) role in preventing apoptosis: The vBCL‐2 and human BIK association
Author(s) -
Yeager Chyenne,
Canfield Jennifer
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.664.15
Subject(s) - bcl 2 family , apoptosis , biology , bcl xl , microbiology and biotechnology , autophagy , programmed cell death , context (archaeology) , virology , genetics , paleontology
Kaposi's Sarcoma‐Associated Herpesvirus (KSHV) is a harmful oncogenic virus that leads to skin cancer commonly found in immunocompromised individuals. KSHV evades host defense systems by targeting signals transduction pathways to suppress autophagy and apoptosis. The BCL‐2 family of proteins controls commitment to apoptosis by regulating mitochondrial outer membrane permeabilization (MOMP). Research has been conducted examining the specific mechanisms and localization of different proteins in the BCL‐2 family such as BAK and BAX, but other proteins like BIK ( BCL‐2 interacting killer) have been far less studied. BIK is a pro‐apoptotic tumor suppressor that is critical n apoptosis induced by cytokines, toxins and viral invasion. Anti‐apoptotic Bcl‐2 family members competitively bind pro‐apoptotic proteins, like BIK, and suppress apoptosis. Although BIK is a known therapeutic target, little is known about the association of BIK with the KSHV BCL‐2 homology, vBCL‐2. In order to learn more about this association, we overexpressed vBCL‐2 in HEK293 cells and carried out subcellular fractionation to localize the protein. We analyzed the physical interaction human BIK and vBCL‐2 using immunoprecipitation under different cellular conditions. We examined the apoptosis mechanism using isolated mitochondria to measure the induction of cytochrome c release in the presence another BCL‐2 family member, BIM, from cells expressing MCL‐1 and MCL‐1 andvBCL‐2. By titrating in BIM and BIK, we can analyze the BIK/vBCL‐2 interactions. Results of these experiments will help elucidate the unique relationship between vBCL‐2 and BIK in the context of mitochondria mediated apoptosis. Definitively elucidating the mechanism, localization, and protein interactions in apoptotic and non‐apoptotic cell death in the presence and absence of vBCL‐2 will guide future therapeutic approaches against KSHV and possibly elucidate other non‐resistant mechanisms to kill cancer cells. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .