The role of exogenous p53 and E6 oncoproteins in in vitro transformation by bovine papillomavirus type 4 (BPV-4): significance of the absence of an E6 ORF in the BPV-4 genome
| Autor: | M. E. Jackson, L. Scobie, M. S. Campo |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
viruses
Cell Mutant Genome Viral Biology Cell Line Mice Open Reading Frames chemistry.chemical_compound Bovine papillomavirus 4 Virology Complementary DNA medicine Animals Humans Gene Bovine papillomavirus 1 Bovine papillomavirus Oncogene Proteins Viral Transfection Fibroblasts biochemical phenomena metabolism and nutrition Cell Transformation Viral biology.organism_classification Molecular biology Repressor Proteins Transformation (genetics) medicine.anatomical_structure chemistry Mutation Cattle Tumor Suppressor Protein p53 DNA |
| Zdroj: | Journal of General Virology. 78:3001-3008 |
| ISSN: | 1465-2099 0022-1317 |
| DOI: | 10.1099/0022-1317-78-11-3001 |
| Popis: | Bovine papillomavirus type 4 (BPV-4) does not possess an E6 ORF. The E6 oncoprotein of human papillomavirus (HPV) binds and degrades the tumour suppressor protein p53, thus contributing to tumour progression. Since BPV-4 lacks E6, it is unknown how the virus evades the tumour suppressor properties of p53 in the induction of tumours of the gastrointestinal tract. Mutations in the p53 gene have been detected both in papillomas and carcinomas, suggesting that p53 dysfunction plays a part in these neoplasias. BPV-4 can transform primary foetal bovine cells (PalFs) in cooperation with an activated ras gene, but the transformed cells are neither immortal nor tumorigenic. Co-transfection with the HPV-16 E6 (16E6) ORF confers immortality but not tumorigenicity. To investigate the role of p53 in BPV-4 cell transformation in vitro, we transfected PalFs and p53-null mouse fibroblasts with BPV-4 DNA in combinations with ras, 16E6 ORF and mutant (V143A) p53 cDNA. Transfection of PalFs with BPV-4 DNA, ras and mutant p53 led to cell immortalization, indicating that 16E6 and mutant p53 are functionally equivalent in conferring immortality. However, co-transfection of PalFs with BPV-4 DNA, ras, and both mutant p53 cDNA and 16E6 ORF resulted in cells which were fully transformed to tumorigenicity. In p53-null mouse fibroblasts, BPV-4 DNA induced transformation by itself, but the transformed cells were incapable of suspension growth. The co-transfection of BPV-4 DNA with 16E6 ORF produced many more transformed colonies and the cells were capable of growing in suspension. In this system, therefore, 16E6 confers anchorage-independence to BPV-4-transformed cells in a p53-independent fashion. |
| Databáze: | OpenAIRE |
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