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MSc Mukund Sharma defended his dissertation titled “Convergence of RAS and PP2A activities on chromatin repressor complexes” on Friday, March 22, 2024.

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Abstract of the doctoral dissertation:

Human cells contain specialized receptors on their surface that communicate with the extracellular factors and pass on the appropriate messages to the interior of the cells. These messages include the timing for cell division and growth.

RAS proteins receive these messages and further pass them on to other proteins finally reaching the nucleus. Specialized proteins in the nucleus (epigenetic proteins) can then unlock the DNA resulting in the tranion of appropriate genes. This results in cell growth and division. Once the job is done another protein (PP2A) signals to lock the DNA stopping further growth. This process of sending messages to the cell interior and its proper implementation is tightly controlled and maintains normal growth and division.

A major cause of cancer is hyperactivation of the growth signal carrier protein (RAS) and inactivation of the signal terminator protein (PP2A). This keeps the DNA in an unlocked state resulting in continuous cell division. It is however not known how RAS and PP2A communicate with the epigenetic proteins that lock or unlock the DNA.

In my Ph.D. thesis, I have tried to understand how RAS and PP2A communicate with the epigenetic proteins. Using specialized tools, I have documented the interaction between RAS, PP2A, and epigenetic proteins. In this study, I found out that both RAS and PP2A can modify some of these proteins resulting in either locking or unlocking of the DNA. This tug-of-war between RAS and PP2A has a major implication for cancer therapy. I identified that by promoting the PP2A-mediated epigenetic communication while inhibiting RAS-mediated, we can restore cellular balance. My study describes a novel cellular communication between a tumor promoter and a tumor suppressor and how it can be utilized in preventing cancer.