Abstract by Colin Muir
Chemistry and Biochemistry
14-3-3ζ binding regulates PTOV1 localization and stability
14-3-3 proteins are a family of phospho-binding proteins that regulate nearly every major cellular function. The isoform 14-3-3ζ interacts with a network of proteins to promote carcinogenesis, and its overexpression is correlated with mortality in multiple cancer types. However, the network of 14-3-3ζ interactors that support oncogenesis remains poorly understood. In this work, we identify a novel interaction between 14-3-3ζ and prostate tumor overexpressed-1 (PTOV1), a transcriptional regulator that also promotes oncogenesis. We identify the phosphorylation sites on PTOV1 responsible for 14-3-3ζ binding and use nuclear fractionation, confocal microscopy, and co-IP experiments to analyze the 14-3-3ζ–PTOV1 interaction. Our data supports a model where 14-3-3ζ sequesters PTOV1 in the cytoplasm to inhibit its nuclear function and protect it from degradation. This work represents the first known mechanism regulating PTOV1 function and could potentially lead to novel therapeutic targets.