Phosphorylation at the carboxy terminus of the 55-kilodalton adenovirus type 5 E1B protein regulates transforming activity.
The 55-kDa product of early region 1B (E1B) of human adenoviruses is required for viral replication and participates in cell transformation through complex formation with and inactivation of the cellular tumor suppressor p53. We have used both biochemical and genetic approaches to show that this 496-residue (496R) protein of adenovirus type 5 is phosphorylated at serine and threonine residues near the carboxy terminus within sequences characteristic of substrates of casein kinase II. Mutations which converted serines 490 and 491 to alanine residues decreased viral replication and greatly reduced the efficiency of transformation of primary baby rat kidney cells. Such mutant 496R proteins interacted with p53 at efficiencies similar to those of wild-type 496R but only partially inhibited p53 transactivation activity. These results indicated that phosphorylation at these carboxy-terminal sites either regulates the inhibition of p53 or regulates some other 496R function required for cell transformation.
Teodoro
J G
JG
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Halliday
T
T
Whalen
S G
SG
Takayesu
D
D
Graham
F L
FL
Branton
P E
PE
D017501:Adenovirus E1B Proteins / Q000235:genetics / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002472:Cell Transformation, Viral / Q000502:physiology*; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D016297:Mutagenesis, Site-Directed; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000032:analysis; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D014158:Transcription, Genetic; D014357:Trypsin / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000032:analysis
D017501:Adenovirus E1B Proteins; D010748:Phosphopeptides; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D014357:Trypsin