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Cells must respond to changing environments by modulating signaling and gene expression patterns to maintain homeostasis, health, and viability. Inappropriate responses lead to disease processes, such as cancer. Despite improvements in targeted treatment options, cancer remains the second leading cause of death in the United States, illustrating the need to develop new highly effective targeted therapies. 14-3-3 interacts with a network of proteins to support signaling pathways promoting oncogenesis, metastasis, growth, cellular survival, and chemoresistance in a variety of cancers, including lung, prostate, and breast. We recently identified prostate tumor overexpressed 1 (PTOV1) as a novel 14-3-3 interacting protein promoting tumorigenic gene expression patterns. We showed that 14-3-3 binding sequesters PTOV1 in the cytoplasm and protects PTOV1 from proteasomal degradation. Using double thymidine block synchronization, we now demonstrate that both PTOV1 phosphorylation and total PTOV1 levels peak in G1, prior to PTOV1 translocating into the nucleus during S phase. These data support our model that 14-3-3-PTOV1 binding maintains PTOV1 in the cytoplasm during G1, where it is stabilized to carry out translational regulation. As the cell enters S phase, loss of phosphorylation and the accompanying loss of 14-3-3 binding allows PTOV1 to translocate into the nucleus, carry out relevant nuclear functions, and then be degraded via the proteasome. Citation Format: Katie L. Pennington, Colten M. McEwan, James Woods, Colin M. Muir, A G Pramoda Sahankumari, Riley Eastmond, Eranga R. Balasooriya, Christina M. Egbert, Katherine K. McCormack, Joshua L. Andersen. 14-3-3 binding during G1 stabilizes and sequesters PTOV1 to the cytoplasm [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1469. |
