DNA and Cell Biology · 1994 · 37 citations · 29 references
Life SciencesMolecular BiologyOncologyGene ExpressionMolecular VirologyTranscriptionCervical CancerCervical Intraepithelial NeoplasiaHuman Papillomavirus InfectionOncogenic VirusesViral Gene ExpressionViral TranscriptionHpv PathogenesisHuman Papillomavirus TreatmentIntracellular Delivery Of Nucleic AcidsIntracellular TargetsPapillomavirus BiologyTranscriptional ActivationTranscriptional Activation DomainsViral Transcription Factors
Papillomaviruses are the causative agents of benign and malignant epithelial tumors of the skin and mucosa. They encode a DNA-binding protein, E2, that regulates viral transcription and replication, making it an important therapeutic target. By deleting the amino-terminal trans-activation domain of human papillomavirus type 16 (HPV-16) E2 while retaining its carboxy-terminal DNA binding and dimerization domain, an E2 repressor (E2R) that efficiently inhibits transcriptional activation by full-length HPV E2 was generated. To deliver this repressor protein into animal cells, we have utilized the human immunodeficiency virus type 1 (HIV-1) Tat protein which itself is taken up efficiently into intact cells. Chimeras of E2R and the cellular uptake domain of Tat specifically inhibited E2-dependent reporter gene expression in COS-7 cells. Treatment of cervical intraepithelial neoplasia cells having episomally replicating HPV-31 DNA with this Tat-E2R protein led to a dose-dependent loss of HPV DNA copies and inhibition of cell growth. Tat-mediated delivery can be a valuable tool for assessing protein function and may allow the development of novel therapeutic proteins having intracellular targets.
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Matthias Dürst, Lutz Gissmann, Hans Ikenberg et al. · Proceedings of the National Academy of Sciences · 1983 · 2K citations · Full text
Tat-mediated delivery of heterologous proteins into cells.
Stephen E. Fawell, J Seery, Yasmin Daikh et al. · Proceedings of the National Academy of Sciences · 1994 · 1.2K citations