Establishing Function of Understudied PRKCQ Kinase in Cellular Regulation and Disease

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Summary/Abstract The overall vision of our research is to gain a comprehensive understanding of the molecular mechanisms driving the function of understudied kinase PRKCQ in order to effectively target it in disease. PRKCQ encodes the protein kinase C (PKC) isozyme PKCq. The PKC family has been intensely investigated in the context of cancer since the discovery in the early 1980s that it is a receptor for the tumor-promoting phorbol esters. This led to the dogma that activation of PKC by phorbol esters promotes carcinogen-induced tumorigenesis. Nonetheless, PKC has been an elusive chemotherapeutic target despite decades of research. We recently established that, contrary to conventional thinking, PKC generally functions as a tumor suppressor, not an oncogene, thus explaining why 30+ years of clinical trials with PKC inhibitors not only failed but, in some cases, worsened patient outcome. In this proposal, we aim to combine bioinformatics, computational, biochemical, and cellular approaches to rapidly understand the molecular details of PKCq and how disease-associated mutations impact function and biology. Uncovering the function of PKCq in oncogenic signaling will inform on how to appropriately target it in cancer therapies.