Myc and YY1 mediate activation of the Surf-1 promoter in response to serum growth factors.
The human Surf-1 and Surf-2 genes are divergently transcribed and share a single bi-directional promoter. The addition of serum growth factors to serum-starved cells activates transcription in the Surf-1 direction, but has no effect on transcription in the Surf-2 direction. Mutations that block the binding of YY1 to a site immediately downstream of the major Surf-1 transcription start point abolish this response to serum factors. Here we show that over-expression of mitogen-activated protein (MAP) kinase phosphatase MKP-1, an inhibitor of the MAP kinase cascade, also blocks the response the Surf-1 promoter to serum factors. YY1 has previously been shown to interact with several transcription factors including Myc. We show that although the Surf-1/Surf-2 promoter does not contain Myc binding sites (E-boxes), Myc over-expression, or the activation of a Myc-oestrogen receptor fusion protein, activates transcription in the Surf-1 direction and that this response to Myc requires a functional YY1 binding site. Our data suggest that the MAP kinase cascade is required for the stimulation of Surf-1 promoter activity and that the Myc-YY1 interaction mediates this response.
Vernon
E G
EG
Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
Gaston
K
K
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000502:physiology*; D050684:E2F Transcription Factors; D050981:Erythroid-Specific DNA-Binding Factors; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011506:Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000502:physiology*; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000502:physiology*; D050986:YY1 Transcription Factor
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050981:Erythroid-Specific DNA-Binding Factors; D006133:Growth Substances; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D056465:Retinoblastoma-Binding Protein 1; C092928:Surf-1 protein; D050680:Transcription Factor DP1; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D020928:Mitogen-Activated Protein Kinases