deleted in liver cancer 1 (dlc1) utilizes a novel binding site for tensin2 ptb domain interaction and is required for tumor-suppressive function删除在肝癌1(dlc1)利用一种新颖的结合位点tensin2 ptb域需要交互和肿瘤抑制功能.pdfVIP

Deleted in Liver Cancer 1 (DLC1) Utilizes a Novel Binding Site for Tensin2 PTB Domain Interaction and Is Required for Tumor-Suppressive Function 1 1 1 1,2 Lo-Kong Chan , Frankie Chi Fat Ko , Irene Oi-Lin Ng , Judy Wai Ping Yam * 1 Liver Cancer and Hepatitis Research Laboratory and SH Ho Foundation Research Laboratories, Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong, China, 2 Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China Abstract Background: Deleted in liver cancer 1 (DLC1) is a Rho GTPase-activating protein (RhoGAP) frequently deleted and underexpressed in hepatocellular carcinoma (HCC) as well as in other cancers. Recent independent studies have shown interaction of DLC1 with members of the tensin focal adhesion protein family in a Src Homology 2 (SH2) domain-dependent mechanism. DLC1 and tensins interact and co-localize to punctate structures at focal adhesions. However, the mechanisms underlying the interaction between DLC1 and various tensins remain controversial. Methodology/Principal Findings: We used a co-immunoprecipitation assay to identify a previously undocumented binding site at 375–385 of DLC1 that predominantly interacted with the phosphotyrosine binding (PTB) domain of tensin2. DLC1- tensin2 interaction is completely abolished in a DLC1 mutant lacking this novel PTB binding site (DLC1DPTB). However, as demonstrated by immunofluorescence and co-immunoprecipitation, neither the focal adhesion localization nor the interaction with tensin1 and C-terminal tensin-like (cten) were affected. Interestingly, the functional significance of