Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many genes which are regulated by growth factors contain a common regulatory element, the serum response element (SRE). Activation of transcription by the SRE involves a ternary complex formed between a ubiquitous factor, serum response factor (SRF), and a second protein, p62/TCF. We used a yeast genetic screen to isolate cDNAs encoding a protein, SAP-1, with the DNA binding properties of p62/TCF. The SAP-1 sequence contains three regions of homology to the previously uncharacterized Elk-1 protein, which also acts as an SRF accessory protein. Only two of these regions are required for cooperative interactions with SRF in the ternary complex. The third contains several conserved sites for the MAP kinases, whose activity is regulated in response to growth factor stimulation. We discuss the potential role of these proteins in regulation of the c-fos SRE.
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PMID:Isolation and characterization of SRF accessory proteins. 810 35

elk-1, an ets related gene codes for a sequence specific DNA binding transcriptional activator which in association with serum response factor (SRF) forms a ternary complex at the c-fos serum response element (SRE). Recently the C-terminal region of both elk-1 and delta elk-1 proteins was shown to undergo phosphorylation by MAP kinases and function as an activator of MAP kinases. Here we show that delta elk-1 and two other elk-1 related proteins SAP-1a and SAP-1b, like elk-1, can function as transcriptional activators. In this report we have localized the transcriptional activation domain of the SAP-1 proteins (STA) to a large portion of the carboxy terminal region and have identified two autonomous transcriptional activation domains in the elk-1 protein, one at the amino (ETA-1) and the other at the carboxy terminal region (ETA-2). delta elk-1 protein contains only the ETA-2 domain indicating differential usage of activation domains as a result of alternative splicing. We can speculate that the ETA-1 domain can function in vivo independent of ETA-2, but the ETA-2 domain can function either in the absence of ETA-1 (as seen in delta elk-1) or in the presence of accessory proteins like SRF. The role of SRF in the activation of the ternary complex might be to bind to the ETA-1 domain, somehow conceal it's activation domain and in the process unmask the ETA-2 domain (for phosphorylation by MAP kinases) and activate transcription. The ETA-1 domain may be functioning as a negative regulatory transcriptional activation domain for ETA-2. These observations suggest that the elk-1 family of proteins may not only regulate fos and MAP kinases but also other elk-1 target genes that are essential for cellular growth control.
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PMID:Transcriptional activation domains of elk-1, delta elk-1 and SAP-1 proteins. 824 51

The ternary complex factor (TCF) subfamily of ETS-transcription factors represent key nuclear targets of the MAP kinase pathways. Members of this subfamily are classified by the presence of several conserved domains for DNA binding, interaction with SRF, interaction with MAP kinases and transcriptional activation. In this study we have isolated a further member of this subfamily (TCF-1) from zebrafish. The protein product of zebrafish TCF-1 (zTCF-1), shares sequence similarity with the mammalian TCFs in all four conserved domains, with highest overall similarity to SAP-1. Zebrafish TCF-1 is expressed throughout zebrafish embryonic development and exhibits typical TCF DNA binding characteristics, with the B-box being required for interaction with SRF. Of the mammalian TCFs, its DNA binding specificity resembles Elk-1. zTCF-1 is a target for both the growth factor/mitogen-activated and stress-activated MAP kinase cascades in vitro and in vivo. However, differential targeting occurs, with the profile of its activation closely resembling that of mammalian SAP-1. Together, our results demonstrate that the TCFs have been functionally conserved during vertebrate development.
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PMID:Molecular characterization of a zebrafish TCF ETS-domain transcription factor. 1063 9