The E2F transcription factor is a cellular target for the RB protein.
Although it is generally believed that the product of the retinoblastoma susceptibility gene (RB1) is an important regulator of cell proliferation, the biochemical mechanism for its action is unclear. We now show that the RB protein is found in a complex with the E2F transcription factor and that only the under phosphorylated form of RB is in the E2F complex. Moreover, the adenovirus E1A protein can dissociate the E2F-RB complex, dependent on E1A sequence also critical for E1A to bind to RB. These sequences are also critical for E1A to immortalize primary cell cultures and to transform in conjunction with other oncogenes. Taken together, these results suggest that the interaction of RB with E2F is an important event in the control of cellular proliferation and that the dissociation of the complex is part of the mechanism by which E1A inactivates RB function.
Chellappan
S P
SP
Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina 27710.
Hiebert
S
S
Mudryj
M
M
Horowitz
J M
JM
Nevins
J R
JR
D017456:Adenovirus Early Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050684:E2F Transcription Factors; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D017456:Adenovirus Early Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D046911:Macromolecular Substances; D009856:Oncogene Proteins, Viral; D010750:Phosphoproteins; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors