Functional dissection of the transcription factor Elk-1.
The ternary complex factor Elk-1 belongs to the Ets oncoprotein family. We demonstrate that this transcription factor is localized predominantly in the nucleus, for which at least two regions of Elk-1 are required. One of these regions is part of the N-terminal ETS-domain, while the other encompasses amino acids 137-157. In conjunction with the ETS-domain, which mediates autonomous binding of Elk-1 to some DNA target sequences, the conserved B-region is both necessary and sufficient for ternary complex formation with the c-fos serum response element and the serum response factor. However, the B-region must be linked to the ETS-domain by a spacer. Furthermore, the B-region impedes autonomous DNA-binding, possibly by masking the ETS-domain. A point mutation within the ETS-domain, homologous to the ts1.1 point mutation of v-Ets in the E26 virus, affects DNA-binding of Elk-1 in a temperature-dependent manner, which by analogy might be causative for the altered phenotype of ts1.1 E26. Finally we show that amino acids 83-428 contribute to Elk-1 mediated transactivation. In particular, the region 376-404 is indispensable for transactivation, while flanking amino acids on both sides are only required for enhancement of transcriptional efficacy.
Janknecht
R
R
Institute for Molecular Biology, Hannover Medical School, Germany.
Zinck
R
R
Ernst
W H
WH
Nordheim
A
A
D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D016762:Genes, fos; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017354:Point Mutation; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D012045:Regulatory Sequences, Nucleic Acid; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins; D013696:Temperature; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D015682:Retroviridae Proteins, Oncogenic; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D004247:DNA