Abstract by Colin Muir
Chemistry and Biochemistry
14-3-3zeta Interacts with TAK1 Under Hypoxic Conditions to Regulate Cell Survival in Cancer
14-3-3 proteins are a family of phospho-binding proteins that regulate nearly every major cellular function. 14-3-3zeta plays a central role in regulating cell response to the nutrient-deprived conditions often experienced by cancer cells, and its overexpression is correlated with mortality in multiple cancer types. Our group has identified TGF-beta-activated kinase-1 (TAK1) and TAK1 binding protein 2 (TAB2) as novel interactors with 14-3-3zeta to regulate cell survival under hypoxic conditions. However, the specific phosphorylation sites and kinases that allow for these interactions to take place are unknown. Additionally, the effects of 14-3-3zeta binding on TAK1 and TAB2 signaling have not yet been fully characterized. In this work, we show that 14-3-3zeta binds to TAK1 on serine 439 under hypoxic conditions.