Independent binding of the retinoblastoma protein and p107 to the transcription factor E2F.
The cellular protein p107 and the retinoblastoma protein (pRB) have many features in common. Most strikingly, they contain homologous protein domains that mediate interaction with the oncoproteins of several small DNA tumour viruses, including adenovirus E1A and SV40 large-T antigen. In cells that do not contain these viral oncoproteins, pRB interacts with the cellular transcription factor E2F or a related protein termed DRTF1. E2F associates with a form of pRB that is found primarily in G1 cells. It seems that the E2F-pRB complex dissociates near the G1-S boundary before the initiation of S phase, releasing free E2F and apparently stimulating the ability of E2F to activate transcription. Cells that express E1A have no or little pRB-E2F complex, presumably because of the association of E1A with pRB. During S phase, E2F forms a second complex that contains cyclin A but apparently lacks pRB. Here, we report that p107 is found in the cyclin A/E2F complex and that this complex also contains p33cdk2. These observations suggest that p107 and pRB cooperate in the regulation of E2F activity, each affecting different stages of the cell cycle. Thus, by binding to pRB and p107, E1A and large-T antigen target two distinct aspects of E2F regulation.
Cao
L
L
Massachusetts General Hospital Cancer Center, Charlestown 02129.
Faha
B
B
Dembski
M
M
Tsai
L H
LH
Harlow
E
E
Dyson
N
N
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D016193:G1 Phase; D006801:Humans; D007163:Immunosorbent Techniques; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D016160:Retinoblastoma Protein / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D016196:S Phase; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D011506:Proteins; C493844:RBL1 protein, human; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; C493735:TFDP1 protein, human; D050680:Transcription Factor DP1; D014157:Transcription Factors