Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation.

TY - JOUR

T1 - Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation.

AU - Helin, K

AU - Wu, C L

AU - Fattaey, A R

AU - Lees, J A

AU - Dynlacht, B D

AU - Ngwu, C

AU - Harlow, E

N1 - Keywords: Adenovirus E2 Proteins; Amino Acid Sequence; Cell Cycle Proteins; Cloning, Molecular; DNA, Complementary; Genes, Reporter; Humans; Models, Genetic; Molecular Sequence Data; Protein Conformation; Recombinant Fusion Proteins; Retinoblastoma Protein; Sequence Analysis; Sequence Homology, Amino Acid; Trans-Activation (Genetics); Transcription Factor DP1; Transcription Factors; Transcription, Genetic; Transfection; Tumor Cells, Cultured

PY - 1993

Y1 - 1993

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 8405995

SN - 0890-9369

VL - 7

SP - 1850

EP - 1861

JO - Genes & Development

JF - Genes & Development

IS - 10

ER -