human papillomavirus-16 e7 interacts with glutathione s-transferase p1 and enhances its role in cell survival人类papillomavirus-16 e7与谷胱甘肽s-transferase p1和增强它的角色在细胞的生存.pdfVIP

Human Papillomavirus-16 E7 Interacts with Glutathione S-Transferase P1 and Enhances Its Role in Cell Survival 1 1 1 2 1 Anna M. Mileo , Claudia Abbruzzese , Stefano Mattarocci , Emanuele Bellacchio , Paola Pisano , 1 3 3 4 4 Antonio Federico , Vittoria Maresca , Mauro Picardo , Alessandra Giorgi , Bruno Maras , M. Eugenia ` 4 1 Schinina , Marco G. Paggi * 1 Department of Development of Therapeutic Programs, CRS, Regina Elena Cancer Institute, Rome, Italy, 2 IRCCS Casa Sollievo della Sofferenza - Mendel Institute, Rome, Italy, 3 San Gallicano Dermatological Institute, Rome, Italy, 4 Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy Abstract Background: Human Papillomavirus (HPV)-16 is a paradigm for ‘‘high-risk’’ HPVs, the causative agents of virtually all cervical carcinomas. HPV E6 and E7 viral genes are usually expressed in these tumors, suggesting key roles for their gene products, the E6 and E7 oncoproteins, in inducing malignant transformation. Methodology/Principal Findings: By protein-protein interaction analysis, using mass spectrometry, we identified glutathione S-transferase P1-1 (GSTP1) as a novel cellular partner of the HPV-16 E7 oncoprotein. Following mapping of the region in the HPV-16 E7 sequence that is involved in the interaction, we generated a three-dimensional molecular model of the complex between HPV-16 E7 and GSTP1, and used this to engineer a mutant molecule of HPV-16 E7 with strongly reduced affinity for GSTP1.