探討癌細胞中WWP2 與 Eps8 之間的交互作用

Abstract

WWP2 (WW domain containing E3 ubiquitin protein ligase 2), also known as atrophin-1-interacting protein 2 (AIP-2), is a member of the NEDD4-like E3 ligases family. It has been indicated to regulate cell proliferation in cancer cells, but the underlying mechanism is still unknown. Eps8 (Epidermal growth factor receptor pathway substrate No.8) is a substrate for both receptor Epidermal growth factor receptor (EGFR) and non-receptor tyrosine kinase (Src). Eps8 regulates cell motility and promotes cell proliferation in cancer cells. Our unpublished data indicates Eps8 may be a WWP2-binding protein and the associated Eps8 is polyubiquitinated. However, the biological function of WWP2-Eps8 interaction is unknown. In this study, we want to address the interacting domains between WWP2 and Eps8. Then, we would like to know whether WWP2 plays a role in Eps8-mediaed oncogenesis. Our data indicated that PPY motif in Eps8 was required to interact with the WW domain(s) in WWP2 by both in vitro GST pull down and co-immunoprecipitation experiments. Furthermore PAF mutation on the PPY sequence of Eps8 impaired Eps8-mediated colony formation in HeLa cell. Thus, WWP2-Eps8 interaction might play an important role in cell growth of cancer cells.