title: Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation.
abstract: 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.
authors.affiliation: Massachusetts General Hospital Cancer Center, Charlestown 02129.
authors.forename: K
authors.initials: K
authors.lastname: Helin
authors.forename: C L
authors.initials: CL
authors.lastname: Wu
authors.forename: A R
authors.initials: AR
authors.lastname: Fattaey
authors.forename: J A
authors.initials: JA
authors.lastname: Lees
authors.forename: B D
authors.initials: BD
authors.lastname: Dynlacht
authors.forename: C
authors.initials: C
authors.lastname: Ngwu
authors.forename: E
authors.initials: E
authors.lastname: Harlow
mesh_terms: 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
chemical_list: 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