title: Interaction of transcription factors with serum response factor. Identification of the Elk-1 binding surface.
abstract: Serum response elements (SREs) play important roles in transforming extracellular signals into specific nuclear responses. The SRE-binding protein, serum response factor (SRF), plays a pivotal role in this process. Several transcription factors have been shown to interact with SRF and thereby create distinct complexes with different regulatory potentials. The ETS domain transcription factor Elk-1 is one such protein and serves to integrate distinct mitogen-activated protein kinase cascades at SREs. Elk-1 uses a short hydrophobic surface presented on the surface of an alpha-helix to interact with SRF. In this study we have used site-directed mutagenesis to identify residues in SRF that comprise the Elk-1 binding surface. The Elk-1 binding surface is composed of residues that lie on a hydrophobic surface-exposed groove located at the junction of the MADS box and C-terminal SAM motif. Different residues are implicated in interactions between SRF and the transcription factor Fli-1, indicating that although some overlap with the Elk-1 binding surface occurs, their interaction surfaces on SRF are distinct. Our data are consistent with the hypothesis that the SRF DNA-binding domain acts as docking site for multiple transcription factors that can bind to small surface-exposed patches within this domain.
authors.affiliation: Department of Biochemistry and Genetics, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, United Kingdom.
authors.forename: Y
authors.initials: Y
authors.lastname: Ling
authors.forename: A G
authors.initials: AG
authors.lastname: West
authors.forename: E C
authors.initials: EC
authors.lastname: Roberts
authors.forename: J H
authors.initials: JH
authors.lastname: Lakey
authors.forename: A D
authors.initials: AD
authors.lastname: Sharrocks
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D026362:Serum Response Factor; D014157:Transcription Factors / Q000378:metabolism*; D050807:ets-Domain Protein Elk-1
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D004247:DNA