The regulatory protein 14-3-3z promotes cellular growth and survival, and high expression levels of 14-3-3z are associated with mortality in multiple cancer types. 14-3-3z binds cellular proteins in a phosphorylation-dependent manner to modulate their functions. We have been characterizing the interactome of 14-3-3z which will likely lead to candidates for novel therapies for chemoresistant cancers. Tumor cells must be able to survive in a variety of stresses within the tumor microenvironment, including hypoxia, which occurs when tumors lack adequate blood supply. Previous data from our lab suggested that 14-3-3z promotes the adaptation of tumor cells to hypoxic stress. Our hypothesis is that hypoxic stress rearranges the interactome of 14-3-3z to focus on interactions that promote hypoxic stress. We have utilized protein mass spectrometry to find likely interactors of 14-3-3z with an emphasis on interactors that are found in high concentrations in hypoxia. We then validated these interactors using Co-IP and Western blot. Using these techniques, we have found several proteins of interest that warrant further exploration, including TAK1 and the TAK1 binding protein, TAB2, both of which are regulators of apoptosis. We are currently mutating potential phosphorylation sites in these proteins to test 14-3-3z binding and regulatory function. We hypothesize that phosphorylated TAK1 and TAB2 bind to 14-3-3z promoting progrowth pathways.
BYU ScholarsArchive Citation
Pennington, Katie; Roshan, Eranga; Andersen, Joshua; and McCormack, Katherine K., "14-3-3zeta Role in Promoting Survival of Cells to Facilitate Progression of Cancer" (2018). Student Publications. 227.
Physical and Mathematical Sciences
Chemistry and Biochemistry
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