title: elk-1 domains responsible for autonomous DNA binding, SRE:SRF interaction and negative regulation of DNA binding.
abstract: The ets oncogene superfamily consists of a family of sequence-specific DNA-binding transcriptional activator proteins. We have previously identified, cloned and characterized one of the divergent ets-related members elk-1 and shown that it codes for a sequence-specific DNA-binding transcriptional activator. We have also shown that elk-1 forms SRF (Serum Response Factor) dependent ternary complex with SRE (Serum Response Element), similar to p62TCF. In this report, we have mapped the DNA-binding domain of the elk-1 protein (EDB, elk-1 DNA Binding domain) to the 76 amino acid ets homology region. We have also mapped the SRF interaction domain of the elk-1 protein (ESI, elk-1 SRF Interaction domain) to the carboxy-terminal region of the EDB domain. Ternary complex formation by elk-1 requires both EDB and ESI domains of the elk-1 protein. Our results also show that the EDB domain of the elk-1 protein (residues 1-89) binds SRE autonomously, unlike full-length elk-1 protein, suggesting the presence of a potential Negative Regulatory DNA binding domain (NRD) which prevents the binding of elk-1 protein to SRE. Interaction of SRF with the ESI domain allows the elk-1 protein to bind to SRE. Thus elk-1 belongs to a class of transcriptional factors that are involved in gene regulation not only by autonomous DNA binding but also by indirect DNA binding through recruitment by cellular factors.
authors.affiliation: Jefferson Cancer Institute, Philadelphia, PA 19107.
authors.forename: V N
authors.initials: VN
authors.lastname: Rao
authors.forename: E S
authors.initials: ES
authors.lastname: Reddy
mesh_terms: D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D026362:Serum Response Factor; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015682:Retroviridae Proteins, Oncogenic; D026362:Serum Response Factor; D014157:Transcription Factors; C050379:oncogene proteins v-ets; D004247:DNA