PloS one, 2009-10, Vol.4 (10), p.e7254
2009
Details
- Autor(en) / Beteiligte
- Titel
- Human papillomavirus-16 E7 interacts with glutathione S-transferase P1 and enhances its role in cell survival
- Ist Teil von
- PloS one, 2009-10, Vol.4 (10), p.e7254
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2009
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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. 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.When expressed in HaCaT human keratinocytes, HPV-16 E7 modified the equilibrium between the oxidized and reduced forms of GSTP1, thereby inhibiting JNK phosphorylation and its ability to induce apoptosis. Using GSTP1-deficient MCF-7 cancer cells and siRNA interference targeting GSTP1 in HaCaT keratinocytes expressing either wild-type or mutant HPV-16 E7, we uncovered a pivotal role for GSTP1 in the pro-survival program elicited by its binding with HPV-16 E7. This study provides further evidence of the transforming abilities of this oncoprotein, setting the groundwork for devising unique molecular tools that can both interfere with the interaction between HPV-16 E7 and GSTP1 and minimize the survival of HPV-16 E7-expressing cancer cells.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0007254Titel-ID: cdi_plos_journals_1292288674
- Format
- –
- Schlagworte
- Amino acids, Antigens, Apoptosis, Bands, Biochemistry/Macromolecular Assemblies and Machines, Cancer, Cell Biology/Cellular Death and Stress Responses, Cell Line, Tumor, Cell Survival, Cell Transformation, Neoplastic, Cervical cancer, Cervical carcinoma, Cervix, Chemical Biology/Macromolecular Chemistry, Cloning, Dermatitis, Drug resistance, Fatty acids, Gene Expression Regulation, Viral, Genetic transformation, Genomes, Glutathione, Glutathione S-Transferase pi - metabolism, Glutathione transferase, Growth factors, Handbooks, Human papillomavirus, Human papillomavirus 16 - metabolism, Humans, Infectious Diseases/Viral Infections, JNK protein, Keratinocytes, Keratinocytes - virology, Kinases, Mass spectrometry, Mass Spectrometry - methods, Mass spectroscopy, Medical prognosis, Molecular Conformation, Mutation, Neisseria meningitidis, Oncogene Proteins, Viral - metabolism, Oncology/Gynecological Cancers, Papillomavirus E7 Proteins, Papillomavirus infections, Papillomaviruses, Peptides, Phosphorylation, Protein Binding, Protein interaction, Protein Interaction Mapping, Protein-protein interactions, Proteins, Repressor Proteins - metabolism, Rodents, Signal transduction, siRNA, Survival, Thiols, Three dimensional models, Transformation, Tumors, Virology/Viruses and Cancer, Vitamin E, Women's Health/Gynecological Cancers