Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation.
The E2F transcription factor has been implicated in the regulation of genes whose products are involved in cell proliferation. Two proteins have recently been identified with E2F-like properties. One of these proteins, E2F-1, has been shown to mediate E2F-dependent trans-activation and to bind the hypophosphorylated form of the retinoblastoma protein (pRB). The other protein, murine DP-1, was purified from an E2F DNA-affinity column, and it was subsequently shown to bind the consensus E2F DNA-binding site. To study a possible interaction between E2F-1 and DP-1, we have now isolated a cDNA for the human homolog of DP-1. Human DP-1 and E2F-1 associate both in vivo and in vitro, and this interaction leads to enhanced binding to E2F DNA-binding sites. The association of E2F-1 and DP-1 leads to cooperative activation of an E2F-responsive promoter. Finally, we demonstrate that E2F-1 and DP-1 association is required for stable interaction with pRB in vivo and that trans-activation by E2F-1/DP-1 heterodimers is inhibited by pRB. We suggest that "E2F" is the activity that is formed when an E2F-1-related protein and a DP-1-related protein dimerize.
Helin
K
K
Massachusetts General Hospital Cancer Center, Charlestown 02129.
Wu
C L
CL
Fattaey
A R
AR
Lees
J A
JA
Dynlacht
B D
BD
Ngwu
C
C
Harlow
E
E
D017502:Adenovirus E2 Proteins / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D017930:Genes, Reporter; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D017502:Adenovirus E2 Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; C493735:TFDP1 protein, human; D050680:Transcription Factor DP1; D014157:Transcription Factors