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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The C2-H2 zinc-finger is a widely occurring DNA binding motif, usually present as tandem repeats. The majority of C2-H2 zinc-finger proteins that have been studied are derived from animals. Here, we characterize a member of a distinct class of plant C2-H2 zinc-finger proteins in detail. A cDNA clone encoding a DNA binding protein from Arabidopsis was isolated by SouthWestern screening. The protein, termed ZAP1 (Zinc-dependent Activator Protein-1), is encoded by a single copy gene, which is expressed to similar levels in root and flower, to a somewhat lower level in stem and to low levels in leaf and siliques. The optimal binding site was determined by random binding site selection, and the consensus sequence found is CGTTGACCGAG. The homology between ZAP1 and other DNA binding proteins is restricted to a repeated region of a stretch of 24 highly conserved amino acids followed by a zinc-finger motif (C-X4-C-X22-23-H-X1-H). The C-terminal zinc-finger region is essential for DNA binding, whereas deletion of the N-terminal one resulted in 2.5-fold reduced binding affinity. Binding of ZAP1 to DNA was abolished by metal-chelating agents. The activation domain as determined in yeast is adjacent to and possibly overlapping with the DNA binding domain. Particle bombardment experiments with plant cells showed that ZAP1 increases expression of a gusA reporter gene that is under control of ZAP1 binding sites. We conclude that ZAP1 is a plant transcriptional activator with a C2-H2 zinc-finger DNA binding domain.
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PMID:Characterization of a zinc-dependent transcriptional activator from Arabidopsis. 897 46

Zinc homeostasis in yeast is controlled primarily through the regulation of zinc uptake. Transcription of the ZRT1 and ZRT2 zinc transporters increases in zinc-limited cells, and this induction is dependent on the ZAP1 gene. We hypothesized previously that ZAP1 encodes a zinc-responsive transcriptional activator. Expression of ZAP1 itself increases in zinc-limited cells. This response is also dependent on ZAP1 function through a potential positive autoregulatory mechanism. In this report, we describe the characterization of zinc-responsive elements (ZREs) in the promoters of the ZRT1, ZRT2, and ZAP1 genes. A ZRE consensus sequence, 5'-ACCYYNAAGGT-3', was identified and found to be both necessary and sufficient for zinc-responsive transcriptional regulation. We also demonstrate that ZREs are DNA binding sites for ZAP1. First, a dominant ZAP1 mutation, ZAP1-1(up), which causes increased expression of ZAP1-regulated genes in zinc-replete cells, exerted its effects specifically through the ZREs. Second, electrophoretic mobility shift assays and in vitro DNase I footprint analyses indicated that ZAP1 binds to ZREs in a sequence-specific fashion. These studies demonstrate that ZAP1 plays a direct role in controlling zinc-responsive gene expression in yeast by binding to zinc-responsive elements in the promoters of genes that it regulates.
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PMID:Regulation of zinc homeostasis in yeast by binding of the ZAP1 transcriptional activator to zinc-responsive promoter elements. 978 67

The Zap1 transcriptional activator of Saccharomyces cerevisiae controls zinc homeostasis. Zap1 induces target gene expression in zinc-limited cells and is repressed by high zinc. One such target gene is ZAP1 itself. In this report, we examine how zinc regulates Zap1 function. First, we show that transcriptional autoregulation of Zap1 is a minor component of zinc responsiveness; most regulation of Zap1 activity occurs post-translationally. Secondly, nuclear localization of Zap1 does not change in response to zinc, suggesting that zinc regulates DNA binding and/or activation domain function. To understand how Zap1 responds to zinc, we performed a functional dissection of the protein. Zap1 contains two activation domains. DNA-binding activity is conferred by five C-terminal C(2)H(2) zinc fingers and each finger is required for high-affinity DNA binding. The zinc-responsive domain of Zap1 also maps to the C-terminal zinc fingers. Furthermore, mutations that disrupt some of these fingers cause constitutive activity of a bifunctional Gal4 DNA-binding domain-Zap1 fusion protein. These results demonstrate a novel function of Zap1 zinc fingers in zinc sensing as well as DNA binding.
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PMID:A dual role for zinc fingers in both DNA binding and zinc sensing by the Zap1 transcriptional activator. 1089 24

OsMADS1 is a MADS box gene controlling flower development in rice. In order to learn more about the function of OsMADS1, we searched for cellular proteins interacting with OsMADS1 employing the yeast two-hybrid system. Two novel proteins with MADS domains, which were named OsMADS14 and OsMADS15, were isolated from a rice cDNA library. OsMADS14 and -15 are highly homologous to the maize MADS box gene ZAP1 which is an orthologue of the floral homeotic gene APETALA1 (AP1). Interactions among the three MADS domain proteins were confirmed by in vitro experiments using GST-fused OsMADS1 expressed in Escherichia coli and in vitro translated proteins of OsMADS14 and -15. We determined which domains in OsMADS1, -14, and -15 were required for protein-protein interaction employing the two-hybrid system and pull-down experiments. While the K domain was essential for protein-protein interaction, a region preceded by the K domain augmented this interaction. Interestingly, the C-terminal region of OsMADS1 functioned as a transcriptional activation domain in yeast and mammalian cells, while, on the other hand, the C domains of OsMADS14 and -15 exhibited only very weak transcriptional activator functionality, if any at all.
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PMID:Two rice MADS domain proteins interact with OsMADS1. 1119 26

We have previously shown that Aspergillus fumigatus is able to grow in zinc-limiting media and that this ability is regulated at transcriptional level by both the availability of zinc and pH. When A. fumigatus grows as a pathogen, it must necessarily obtain zinc from the zinc-limiting environment provided by host tissue. Accordingly, the regulation of zinc homeostasis by some zinc-responsive transcriptional regulator in A. fumigatus must be essential for fungal growth within tissues of an immunocompromised host and, in turn, for pathogenicity. Here we provide evidence of the role of the zafA gene in regulating zinc homeostasis and its relevance in the virulence of A. fumigatus. Thus, we observed that (i) zafA can functionally replace the ZAP1 gene from Saccharomyces cerevisiae that encodes the zinc-responsive transcriptional activator Zap1 protein; (ii) the expression of zafA itself is induced in zinc-limiting media and repressed by zinc; (iii) deletion of zafA impairs the germination and growth capacity of A. fumigatus in zinc-limiting media; and (iv) the deletion of zafA abrogates A. fumigatus virulence in a murine model of invasive aspergillosis. In light of these observations, we concluded that ZafA is a zinc-responsive transcriptional activator that represents an essential attribute for A. fumigatus pathogenicity. Consequently, ZafA may constitute a new target for the development of chemotherapeutic agents against Aspergillus, because no zafA orthologues have been found in mammals.
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PMID:The regulation of zinc homeostasis by the ZafA transcriptional activator is essential for Aspergillus fumigatus virulence. 1754 14