Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ets oncogene superfamily consists of a family of sequence-specific DNA-binding proteins that activate transcription. We have previously identified two new members of the ets oncogene superfamily, namely elk-1 and elk-2. In this report we show that the recombinant elk-1 protein expressed in bacteria, like the c-ets-1 proto-oncogene, binds in a sequence-specific manner to Moloney murine sarcoma virus long terminal repeat, E74 target sequences and the PEA3 motif (polyoma enhancer), but does not bind to PU box sequences. Thus analysis of the DNA-binding specificity of ets-related proteins supports the view that different members show similar DNA-binding specificity, which is a general feature of the homeobox proteins. Our data using the chloramphenicol acetyltransferase gene linked to a thymidine kinase promoter containing multimers of the elk-1 target sequence indicates that elk-1 functions as a transcriptional activator. Interestingly, although elk-1 is the most divergent of all the members of the ets gene family, it shows very close similarities with c-ets-1 in some of its sequence-specific DNA-binding specificities. Here, we propose a new function for the elk-1 gene to act as a transcriptional activator of retroviruses and DNA tumor viruses.
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PMID:A divergent ets-related protein, elk-1, recognizes similar c-ets-1 proto-oncogene target sequences and acts as a transcriptional activator. 174 Nov 66

The ets proto-oncogene family is a group of sequence-related genes whose normal cellular function is unknown. In a study of cellular proteins involved in the transcriptional regulation of murine retroviruses in T lymphocytes, we have discovered that a member of the ets gene family encodes a sequence-specific DNA-binding protein. A mouse ets-1 cDNA clone was obtained by screening a mouse thymus cDNA expression library with a double-stranded oligonucleotide probe representing 20 bp of the Moloney murine sarcoma virus (MSV) long terminal repeat (LTR). The cDNA sequence has an 813-bp open reading frame (ORF) whose predicted amino acid sequence is 97.6% identical to the 272 carboxy-terminal amino acids of the human ets-1 protein. The ORF was expressed in bacteria, and the 30-kD protein product was shown to bind DNA in a sequence-specific manner by mobility-shift assays, Southwestern blot analysis, and methylation interference. A mutant LTR containing four base pair substitutions in the ets-1 binding site was constructed and was shown to have reduced binding in vitro. Transcriptional efficiency of the MSV LTR promoter containing this disrupted ets-1 binding site was compared to the activity of a wild-type promoter in mouse T lymphocytes in culture, and 15- to 20-fold reduction in expression of a reporter gene was observed. We propose that ets-1 functions as a transcriptional activator of mammalian type-C retroviruses and speculate that ets-related genes constitute a new group of eukaryotic DNA-binding proteins.
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PMID:Sequence-specific DNA binding of the proto-oncoprotein ets-1 defines a transcriptional activator sequence within the long terminal repeat of the Moloney murine sarcoma virus. 216 47

ets oncogene superfamily consists of a family of transcriptional factors that functions as activators and/or repressors. Previously, we have identified a member of this ets superfamily namely erg, ets related gene. erg gene was shown to code for at least two proteins erg-1 and erg-2 because of alternative splicing and alternative usage of initiation codon. In this report we show that erg gene codes for an additional erg variant protein, erg-3 as a result of differential splicing which results in the insertion of 24 amino acids in the coding region of erg-2 protein. RNAase protection analysis revealed that erg-3 transcripts are expressed in a variety of cells. Erg-3 was also found to activate the transcription of the reporter TK-CAT gene linked to erg target sequences suggesting that erg-3 codes for a sequence specific transcriptional activator.
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PMID:Differentially spliced erg-3 product functions as a transcriptional activator. 829 Feb 79

Ewing's sarcoma family of tumors (ESFT) affect patients between the ages of 3 and 40 years, with most cases occurring in the second decade of life. ESFTs are characterized by a translocation that occurs in 95% of tumors. This translocation joins the Ewing's sarcoma gene (EWS) located on chromosome 22 to an ets family gene; either friend leukemia insertion (FLI)1 located on chromosome 11, t(11;22), or ets-related gene (ERG) located on chromosome 21, t(21;22). The EWS-FLI1 fusion transcript encodes a 68 kDa protein with two primary domains. The EWS domain is a potent transcriptional activator, while the FLI1 domain contains a highly conserved ets DNA binding domain. ESFT presents a clinical challenge, especially in patients with metastatic disease in which dose-intensifying chemotherapy with bone-marrow transplantation does not improve survival. EWS-FLI1 is only present in ESFT cells and does not exist in any normal cell of the body. Experiments using ESFT cell lines or animal xenograft models have proven that EWS-FLI1 is required for tumor survival. Therefore, ESFT contains a unique protein generated by a tumor-specific translocation that has great potential as a molecular target for therapy. However, therapeutic applications directed towards eliminating or inactivating EWS-FLI1 have not reached the clinic. EWS-FLI1 has been a very difficult molecule to directly analyze in vitro due to poor solubility. Recent advances in generating recombinant EWS-FLI1 and novel data on the cellular functions of EWS-FLI1 should enhance progress towards understanding and application.
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PMID:Ewing's sarcoma oncoprotein EWS-FLI1: the perfect target without a therapeutic agent. 1655 28