Role of phosphorylation near the amino terminus of adenovirus type 5 early region 1A proteins

• Published in: Journal of general virology 1993-04, Vol.74 (4), p.583-595
• Main Authors: Dumont, Daniel J, Marcellus, Richard C, Bayley, Stanley T, Branton, Philip E
• Format: Article
• Language: English
• Subjects: Adenovirus E1A Proteins - metabolism; Adenoviruses, Human - metabolism; Animals; Biological and medical sciences; Cell Compartmentation; Cell Transformation, Viral; Enhancer Elements, Genetic; Fundamental and applied biological sciences. Psychology; Humans; In Vitro Techniques; Microbiology; Mutagenesis, Site-Directed; Nuclear Proteins - metabolism; Peptide Fragments - chemistry; Phosphoproteins - metabolism; Phosphorylation; Rats; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Structure-Activity Relationship; Virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/0022-1317-74-4-583

1 Molecular Virology and Immunology Programme, Department of Pathology and 2 Department of Biology, McMaster University, Hamilton, Ontario, Canada L8N 3Z5 and 3 Department of Biochemistry, McGill University, McIntyre Medical Sciences Building, 3655 Drummond Street, Montreal, Quebec, Canada H3G 1Y6 Human adenovirus early region 1A (E1A) proteins act as transcriptional regulators and function in the control of DNA synthesis and cell transformation. Little is known about how these viral products are functionally regulated. E1A proteins of adenovirus serotype 5 (Ad5) are phosphorylated at several serine residues and previous studies had indicated that both Ser-89 and Ser-219 are substrates for one or more of the cdc2 family of cell cycle kinases. A second residue near the amino terminus, Ser-96, may also be a site. Although phosphorylation of Ser-89 causes a major shift in gel mobility, the effect on E1A biological activity is unclear. In the present studies we have shown by mutational analysis that phosphorylation at Ser-89 also regulates phosphorylation at Ser-96, suggesting that the gel mobility shift is the result of multiple phosphorylation events. Phosphorylation at Ser-89 did not seem to affect E1A-mediated repression of the simian virus 40 enhancer or trans-activation of the E3 promoter significantly, but it did appear to have a modest but significant effect on transformation of primary baby rat kidney cells. Present address: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5. Received 23 June 1992; accepted 3 November 1992.