Interaction of the HPV E7 proteins with the pCAF acetyltransferase.
Most cervical carcinomas express the E6 and E7 proteins of a high-risk human papillomavirus (HPV). These proteins affect growth control by interfering with the functions of cell regulatory proteins, promoting oncogenic transformation. A key target of E7 is the tumor suppressor protein pRb, which directly interacts with E7. However, binding ... to additional cellular regulatory proteins is clearly required for oncogenesis, as mutants of E7 have been identified that bind to pRb, yet fail to transform efficiently. Here we demonstrate the interaction of the HPV 6, 16 and 18 E7 proteins with the pCAF acetyltransferase, which has been reported to function as a coactivator for a variety of transcription factors including p53. Mutation of a highly conserved leucine residue within the zinc finger region of HPV 16 E7 disrupts binding to pCAF and also impairs transformation and transcriptional activation. HPV 16 E7 interacts with the acetyltransferase domain of pCAF, and reduces its acetyltransferase activity in vitro. Our analysis of the interaction between the pCAF acetyltransferase and E7 provides new insight into the mechanisms by which the E7 oncoproteins can alter cellular gene expression and growth.
Mesh Terms:
Acetylation, Acetyltransferases, Animals, COS Cells, Cell Line, Cell Transformation, Viral, Cercopithecus aethiops, DNA-Binding Proteins, Gene Expression Regulation, Viral, Histone Acetyltransferases, Histones, Humans, Macromolecular Substances, Oncogene Proteins, Viral, Papillomaviridae, Papillomavirus E7 Proteins, Protein Binding, Protein Interaction Mapping, Protein Kinases, Protein Processing, Post-Translational, Protein Structure, Tertiary, Recombinant Fusion Proteins, Risk, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcriptional Activation, Transfection, Two-Hybrid System Techniques, Zinc Fingers
Acetylation, Acetyltransferases, Animals, COS Cells, Cell Line, Cell Transformation, Viral, Cercopithecus aethiops, DNA-Binding Proteins, Gene Expression Regulation, Viral, Histone Acetyltransferases, Histones, Humans, Macromolecular Substances, Oncogene Proteins, Viral, Papillomaviridae, Papillomavirus E7 Proteins, Protein Binding, Protein Interaction Mapping, Protein Kinases, Protein Processing, Post-Translational, Protein Structure, Tertiary, Recombinant Fusion Proteins, Risk, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcriptional Activation, Transfection, Two-Hybrid System Techniques, Zinc Fingers
Oncogene
Date: Jun. 19, 2003
PubMed ID: 12813456
View in: Pubmed Google Scholar
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