The regions of the retinoblastoma protein needed for binding to adenovirus E1A or SV40 large T antigen are common sites for mutations.
The protein product of the retinoblastoma (RB) gene is thought to function in a pathway that restricts cell proliferation. Recently, transforming proteins from three different classes of DNA tumor viruses have been shown to form complexes with the RB protein. Genetic studies suggest that these interactions with the RB protein are important steps in transformation by these viruses. In order to understand better the function of the RB-viral oncoprotein complexes, we have mapped the regions of the RB protein that are necessary for these associations. Two non-contiguous regions of RB were found to be essential for complex formation with adenovirus E1A or SV40 large T antigen. These two regions are found between amino acids 393 and 572 and 646 and 772. Interestingly, these binding sites on RB overlap with the positions of naturally occurring, inactivating mutations of the RB gene. These results strongly suggest that these viral oncoproteins are targeting a protein domain that is an important site in the normal function of the RB protein.
Hu
Q J
QJ
Cold Spring Harbor Laboratory, NY 11724.
Dyson
N
N
Harlow
E
E
D017456:Adenovirus Early Proteins; D001483:Base Sequence; D001665:Binding Sites; D002872:Chromosome Deletion; D004268:DNA-Binding Proteins / Q000378:metabolism; D005134:Eye Neoplasms / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D014176:Protein Biosynthesis; D012175:Retinoblastoma / Q000235:genetics; D016160:Retinoblastoma Protein; D013489:Suppression, Genetic
D017456:Adenovirus Early Proteins; D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D009856:Oncogene Proteins, Viral; D010750:Phosphoproteins; D016160:Retinoblastoma Protein