Abstract by James Woods
Chemistry and Biochemistry
14-3-3 regulates the localization and stability of PTOV1
Prostate tumor overexpressed protein 1 (PTOV1) has been implicated as a driver in several types of cancer. Unfortunately, the regulatory mechanisms that control PTOV1 are not well understood. In this study, we identified a previously unknown interaction between PTOV1 and 14-3-3 via immunoprecipitation-mass spectrometry. Using site directed mutagenesis, we identified two phosphorylation sites on PTOV1 that mediate this interaction with 14-3-3. Our data shows that when either of these residues is mutated, PTOV1 translocates to the nucleus and total levels of PTOV1 decrease. Further experiments showed that PTOV1 is cleared from the cell via HUWE1-catalyzed ubiquitination and proteasomal degradation. These data suggest a model where 14-3-3 sequesters PTOV1 in the cytoplasm and prevents PTOV1 degradation via HUWE1. Going forward, this understanding of PTOV1 biology may inform future efforts to develop targeted therapies for PTOV1 expressing cancers.