Delta elk-1, a variant of elk-1, fails to interact with the serum response factor and binds to DNA with modulated specificity.
The ets oncogene superfamily codes for a family of transcriptional factors that are involved in gene regulation not only by autonomous DNA binding but also by indirect DNA binding through interaction with cellular factors. We have previously shown that a member of this superfamily, elk-1, is a sequence specific transcriptional activator, which forms a serum response factor (SRF) dependent ternary complex with serum response element (SRE) similar to p62TCF. We describe here an alternatively spliced variant of elk-1 named delta elk-1, which has lost the SRF interaction domain, negative regulatory DNA binding domain, and part of the elk-1 DNA binding domain. This variant elk-1 protein has lost the capacity to form a SRF dependent ternary complex with SRE and to activate fos transcription. Since this splice variant lacks part of the ets DNA binding domain, it binds to DNA with a specificity that is different from that of the full length elk-1 protein. Therefore differential splicing within the DNA binding and protein-protein interaction domains of transcriptional factors can generate proteins with modulated DNA binding specificities and transcriptional regulation. Thus it is conceivable that variant elk-1 might function by competing for some of the elk-1 target sequences (like SRE) and thereby block the transcriptional activation of fos by SRF and elk-1. Alternately, variant elk-1 protein may be the repressor, recruited by the SRE bound SRF for c-fos repression, or it may have an altogether different function. Therefore, elk-1 appears to fall in the category of genes that encode activators and repressors through the mechanism of differential splicing.
Rao
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Department of Microbiology and Immunology, Jefferson Cancer Institute, Philadelphia, Pennsylvania 19107-5541.
Reddy
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ES
D016475:3T3 Cells; D017398:Alternative Splicing; D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000378:metabolism*; D026362:Serum Response Factor; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism*; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; C494113:Elk1 protein, mouse; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; D026362:Serum Response Factor; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D004247:DNA