title: Adenovirus E1A makes two distinct contacts with the retinoblastoma protein.
abstract: Two regions near the amino terminus of the adenovirus E1A protein, which were first identified by sequence conservation among various adenovirus serotypes, have been shown by genetic studies to be essential for E1A-mediated transformation. These same regions are also required for interaction with a number of cellular proteins, including the retinoblastoma protein (pRB). Using synthetic peptides corresponding to portions of these conserved regions, we show that each region can bind independently to pRB. These interactions were observed in both competition and binding assays. In both types of assay, region 2 peptides (E1A amino acids 115 to 132) bound pRB with higher affinity than did region 1 peptides (E1A amino acids 37 to 54), while a peptide combining region 1 and 2 sequences consistently provided the highest-affinity interaction. Cross-blocking experiments using region 1 peptides and region 2 peptides suggested that these two regions of E1A make distinct contacts with pRB. These data support the notion that the pRB-binding domain of E1A contains at least two functional elements.
authors.affiliation: Massachusetts General Hospital Cancer Center, Charlestown, 02129.
authors.forename: N
authors.initials: N
authors.lastname: Dyson
authors.forename: P
authors.initials: P
authors.lastname: Guida
authors.forename: C
authors.initials: C
authors.lastname: McCall
authors.forename: E
authors.initials: E
authors.lastname: Harlow
mesh_terms: D017456:Adenovirus Early Proteins; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*
chemical_list: D017456:Adenovirus Early Proteins; D009856:Oncogene Proteins, Viral; D016160:Retinoblastoma Protein