Abstract A61: 14-3-3gamma transforming ability is determined by a motif outside the conserved phosphoamio-acid binding domain

Abstract

Abstract The 14-3-3 proteins are a set of seven highly conserved scaffolding proteins that have been implicated as having a role in human tumorigenesis. However, despite the striking similarity of amino acid sequences and structures of the eukaryotic 14-3-3 family of proteins, there is increasing evidence that the seven human isoforms manifest disparate functions. For instance 14-3-3gamma functions as an oncogene and 14-3-3sigma acts as a tumor suppressor. To gain insight into how specific functions are manifested we constructed chimeric proteins by swaping various regions between gamma and sigma. Chimeric proteins were then utilized in NIH3T3 cell transformation assays. We found that transforming ability was associated with a small variable 40 amino acid region in the N-terminus of the gamma protein and that the transforming ability of gamma was dominant to the tumor suppressor activity of sigma. Importantly, the transforming motif was located outside the conserved 14-3-3 phosphoamino acid binding motif. Hence, transforming ability of 14-3-3 proteins is determined by a variable region that does not involve the phosphoamino acid binding site. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A61.