Mentors: Lisa Cucolo, Guo Wei
In multicellular organisms, apoptosis (or “programmed cell death”) is induced by stimuli such as DNA damage or activation of cell-death receptors by external signals. The mitochondrial protein MCL1 is an anti-apoptotic protein overexpressed in many cancer cell lines. MCL1 binds to and sequesters pro-apoptotic proteins to prevent cell death. Co-immunoprecipitation (co-IP) of MCL1 followed by mass spectrometry previously identified 72 proteins, including BAP31. BAP31 is a pro-apoptotic protein that – when overexpressed – induces cell death.
Michael and his mentors showed that ectopic expression of BAP31 led to cell death in an MCL1-dependent human cancer cell line (EVAST). BAP31 expression caused caspase activation (which is associated with apoptosis), and this activation was rescued by overexpression of MCL1. Michael then performed co-IP experiments to show that BAP31 indeed interacts with MCL1 in EVSAT cells. Future directions include further validation and characterization of MCL1 binding to BAP31, and discovering a potential drug that could disrupt this binding & release BAP31 (and thus induce apoptosis in cancer cells).
Michael, a senior at the John D. O’Bryant School, determined that the protein BAP31 (which induces programmed cell death) is inhibited in cancer cells by physically interacting with the protein MCL1.