Date of Award
MS in Biology
TRPM6 and TRPM7 are two divalent metal cation channels that also possess a serine/threonine kinase domain. They both play critical roles in cellular and organismal metal homeostasis, and are necessary for proper embryonic development and human health. They may function independently in homomeric units, or act together as heterotetramers that display unique characteristics compared to the homomeric channels. These channel-kinases have increasingly been linked to cancer, displaying altered expression levels in a variety of human cancers and contributing to disease progression. Prior work has shown that TRPM6 and TRPM7 can participate in cancer-related signaling pathways. Here, the potential for TRPM6 and TRPM7 to regulate the key tumor suppressor p53 is examined. Through ectopic expression of proteins of interest, we sought to determine effects of TRPM6 and TRPM7 on p53 stability and activity, demonstrate potential interactions between TRPM6 and members of the p53 pathway, and study the behavior of the TRPM6 kinase domain under cellular stress. The results indicated that TRPM6 and TRPM7 can stimulate p53 activity, possibly via phosphorylation of p53 by the TRPM6 kinase domain, as well as influence p53 stability, and that TRPM6 can interact directly with both p53 and its negative regulator MDMX. These findings lay the groundwork for future research into how TRPM6 and TRPM7 regulate the p53 pathway and may inform the role played by these channel-kinases in human cancers.
Whitbread, Thomas, "REGULATION OF p53 BY TRPM6 AND TRPM7" (2023). Theses and Dissertations. 592.
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