Abstract by Katherine McCormack
Chemistry and Biochemistry
Interaction of TAK1 and TAB2 on 14-3-3z
The regulatory protein 14-3-3z promotes cellular growth and survival; high expression of 14-3-3z is associated with mortality and chemoresistance in multiple cancers. 14-3-3z binds phosphorylated proteins to modulate their functions. The characterization of the 14-3-3z interactome will potentially lead to novel therapies for chemoresistant cancers. Tumor cells adapt to survive a variety of stresses within their microenvironment, including hypoxia, which occurs when tumors lack adequate blood supply. 14-3-3z has been implicated in promoting the adaptation of tumor cells to hypoxic stress. Our hypothesis is that the interactome of 14-3-3z rearranges to promote growth under hypoxic stress. We have used protein mass spectrometry to find proteins that interact with 14-3-3z in hypoxia, and then validated the interactions using Co-IP and Western blots. We have identified TAK1 and TAB2, which are apoptosis regulators, as hypoxia-induced interactors of 14-3-3z. We hypothesize that TAK1 and TAB2 bind to 14-3-3z to promote pro-growth pathways. We are currently mutating potential phospho sites on TAB2 and TAK1 to test 14-3-3z binding and regulatory function.