Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein

• Published in: Nature (London) Vol. 357; no. 6373; pp. 82 - 85
• Main Authors: Yew, P. Renee, Berk, Arnold J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 07.05.1992; Nature Publishing Group
• Subjects: adenovirus; Adenovirus Early Proteins; Animals; Biological and medical sciences; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Viral - physiology; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Gene Expression; Genetics; Molecular and cellular biology; Molecules; Mutation; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - physiology; Protein Binding; Proteins; Rats; Structure-Activity Relationship; Transcriptional Activation; Tumor Suppressor Protein p53 - antagonists & inhibitors; Tumor Suppressor Protein p53 - physiology; Adenoviridae; Rat; Transcription; Gene product; Rodentia; Molecular interaction; Cell transformation; Host virus relation; Mechanism; Kidney; Virus; Vertebrata; Adenovirus 2; Mammalia; Cell line; Mastadenovirus; Inhibition; Tumor suppressor gene
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/357082a0

The cellular phosphoprotein p53 inhibits progression through the mammalian cell cycle. Both p53 alleles are frequently mutated in human tumours, indicating that p53 is a tumour suppressor. Recent studies have suggested that p53 functions as a transcriptional activator, but the significance of this activity in cell-cycle control has not been established. The adenovirus 2 (Ad2) early 1B (E1B) 55K protein binds to p53 in transformed cells and contributes to oncogenic transformation by Ad2 (refs 10-12). Here we report that mutants of E1B 55K and wild-type Ad12 E1B 54K proteins show a strong correlation between their ability to inhibit p53-mediated transcriptional activation and their ability to cooperate with adenovirus E1A protein in the transformation of primary cells. These results indicate that p53 probably inhibits cell cycling by functioning as a transcription factor.