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)

Fruiting body development of Myxococcus xanthus is propelled by temporal gene expression directed via stage-specific intercellular signaling pathways. M. xanthus exhibits social behaviors during its complex life cycle and is a potential source for production of natural products such as secondary metabolites. The numerous signaling pathways of M. xanthus consist of not only the two-component His-Asp phosphorelay system (TCS) but also protein Ser/Thr kinases (PSTKs) that regulate gene expression, motility and multicellular development. Recent studies have uncovered the unique molecular regulatory mechanism of MrpC, a transcription factor essential for fruiting body development and sporulation. mrpC expression is activated early in development by MrpB, which belongs to the NtrC family of TCS. MrpC, is, in turn, a transcriptional activator of fruA that encodes another key transcription factor, FruA. FruA is essential for fruiting body development and sporulation and regulates positively and negatively the synthesis of many developmental proteins. In addition, expression of mrpC during vegetative growth is kept at a low level by the PSTK Pkn8-Pkn14 kinase cascade which negatively regulates MrpC-binding activity to its own promoter. Therefore, M. xanthus utilizes a novel dual system with both eukaryotic PSTK cascade and prokaryotic TCS signaling systems to tightly and precisely regulate MrpC levels, which activate timely fruA expression and propel fruiting body development and sporulation.
 ...
PMID:Dual regulation with Ser/Thr kinase cascade and a His/Asp TCS in Myxococcus xanthus. 1879 84

gamma-Secretase is a multisubunit membrane protein complex consisting of presenilin (PS1), nicastrin (NCT), anterior pharynx-1, and presenilin enhancer 2. To analyze the activity of familial Alzheimer disease mutants and to understand the roles of the subunits, we established a yeast transcriptional activator Gal4p system with artificial gamma-secretase substrates containing amyloid precursor protein or Notch fragments. The gamma-secretase activities were evaluated by transcriptional activation of reporter genes upon Gal4p release from the membrane-bound substrates, i.e. growth of yeast on histidine and adenine, or beta-galactosidase assay. We screened and evaluated gamma-secretase mutants using this reconstitution system in yeast, which does not possess endogenous gamma-secretase activity. When we introduced familial Alzheimer mutants of PS1 in this system, their activities were shown to be loss of function. Although the protease activity of wild type PS1 depends on the other three subunits introduced, we obtained 15 new PS1 mutants, which are active in the absence of NCT. They possessed a S438P mutation at the ninth transmembrane domain (TM9) together with one missense mutation distributed through transmembrane and loop regions. These mutations were not related to familial Alzheimer mutations of PS1 as identified so far. The S438P mutant was partially active but required other mutations for full activation. Results of the beta-galactosidase assay suggested that they have wild type protease activities, which were further confirmed by the endoproteolysis of PS1, amyloid beta peptides, and Notch intracellular domain production in mammalian cells. These results suggest that NCT is dispensable for the protease activity of gamma-secretase.
 ...
PMID:Nicastrin is dispensable for gamma-secretase protease activity in the presence of specific presenilin mutations. 1925 53

The maltose transporter gene is situated at the MAL locus, which consists of genes for a transporter, maltase, and transcriptional activator. Five unlinked MAL loci (MAL1, MAL2, MAL3, MAL4, and MAL6) constitute a gene family in Saccharomyces cerevisiae. The expression of the maltose transporter is induced by maltose and repressed by glucose. The activity of the maltose transporter is also regulated post-translationally; Mal61p is rapidly internalized from the plasma membrane and degraded by ubiquitin-mediated proteolysis in the presence of glucose. We found that S. cerevisiae strain ATCC20598 harboring MAL21 could grow in maltose supplemented with a non- assimilable glucose analogue, 2-deoxyglucose, whereas strain ATCC96955 harboring MAL61 and strain CB11 with MAL31 and AGT1 could not. These observations implied a Mal21p-specific resistance against glucose-induced degradation. Mal21p found in ATCC20598 has 10 amino acids, including Gly-46 and His-50, that are inconsistent with the corresponding residues in Mal61p. The half-life of Mal21p for glucose-induced degradation was 118 min when expressed using the constitutive TPI1 promoter, which was significantly longer than that of Mal61p (25 min). Studies with mutant cells that are defective in endocytosis or the ubiquitination process indicated that Mal21p was less ubiquitinated than Mal61p, suggesting that Mal21p remains on the plasma membrane because of poor susceptibility to ubiquitination. Mutational studies revealed that both residues Gly-46 and His-50 in Mal21p are essential for the full resistance of maltose transporters against glucose-induced degradation.
 ...
PMID:Gly-46 and His-50 of yeast maltose transporter Mal21p are essential for its resistance against glucose-induced degradation. 1935 40

Friends and colleagues remember John N. Brady, Ph.D., Chief of the Virus Tumor Biology Section of the Laboratory of Cellular Oncology, who died much too young at the age of 57 on April 27, 2009 of colon cancer. John grew up in Illinois and received his Ph.D. with Dr. Richard Consigli at Kansas State University studying the molecular structure of polyomavirus. In 1984 John came to the National Institutes of Health as a Staff Fellow in the laboratory of Dr. Norman Salzman, Laboratory of Biology of Viruses NIAID, where he was among the first to analyze SV40 transcription using in vitro transcription systems and to analyze regulatory sequences for SV40 late transcription. He then trained with Dr. George Khoury in the Laboratory of Molecular Virology NCI, where he identified SV40 T-antigen as a transcriptional activator protein. His research interests grew to focus on the human retroviruses: human T-cell lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV), analyzing how interactions between these viruses and the host cell influence viral gene regulation, viral pathogenesis and viral transformation. His research also impacted the fields of eukaryotic gene regulation and tumor suppressor proteins. John is survived by his wife, Laraine, and two sons, Matt and Kevin.
 ...
PMID:Memories of John N. Brady: scientist, mentor and friend. 1945 30

In low GC content gram-positive bacteria, the HPr protein is the master regulator of carbon metabolism. HPr is a key component of the phosphoenolpyruvate (PEP):sugar phosphotransferase system that interacts with and/or phosphorylates proteins relevant to carbon catabolite repression. HPr can be phosphorylated by two distinct kinases as follows: the bifunctional enzyme HPr kinase/Ser(P)-HPr phosphorylase (HprK/P) phosphorylating the serine 46 residue (Ser(P)-HPr) and acting as a phosphorylase on Ser(P)-HPr; and the PEP-requiring enzyme I (EI) generating histidine 15-phosphorylated HPr (His(P)-HPr). The various HPr forms interact with numerous enzymes and modulate their activity. By carrying out a genome-wide yeast two-hybrid screen of a Bacillus subtilis library, we identified a novel HPr-interacting protein, the transcriptional activator YesS, which regulates the expression of pectin/rhamnogalacturonan utilization genes. Remarkably, yeast tri-hybrid assays involving the ATP-dependent HprK/P and the PEP-dependent EI suggested that YesS interacts with HPr and His(P)-HPr but not with Ser(P)-HPr. These findings were confirmed by in vitro interaction assays using the purified HPr-binding domain of the YesS protein. Furthermore, pectin utilization and in vivo YesS-mediated transcriptional activation depended upon the presence of His(P)-HPr, indicating that HPr-mediated YesS regulation serves as a novel type of carbon catabolite repression. In the yeast two-hybrid assays, B. subtilis HprK/P and EI were active and specifically recognized their substrates. Both kinases formed long lived complexes only with the corresponding nonphosphorylatable mutant HPr. These findings suggest that two-hybrid assays can be used for the identification of unknown kinases of phosphorylated bacterial proteins detected in phosphoproteome analyses.
 ...
PMID:Transcriptional activator YesS is stimulated by histidine-phosphorylated HPr of the Bacillus subtilis phosphotransferase system. 1965 70

The BZLF1 gene-encoded protein, Zta (EB1, ZEBRA), is a key transcriptional activator of induction of the lytic cycle of EBV. Zta; it contains a basic region with homology to the DNA binding domains of the AP-1 family. In this study, an alternatively spliced BZLF1 (Delta BZLF1) cDNA lacking exon 2, which encodes the DNA-binding domain of Zta, was isolated from B95-8 marmoset cell line releasing EBV. The cDNA was inserted into a prokaryotic expression vector pET-28a+. The His-tagged recombinant protein was overproduced in E. coli BL21(DE3) and purified by nickel affinity chromatography. The purified fraction was characterized by Western blot and MALDI-TOF-MS analysis and used as an antigen to immunize mice. The antibody against Delta Zta can recognize both denatured and natural Zta protein. The Delta Zta protein and its antibody can be used to further investigate its unknown functions.
 ...
PMID:Construction and expression of a spliced variant of Epstein-Barr virus bzlf1 and preparation of its polyclonal antibody. 2002 94

GvpE is the transcriptional activator of the gvp gene cluster involved in gas vesicle formation in Haloabacterium salinarum. A 20-nucleotide sequence is required for the GvpE-mediated activation of the two oppositely oriented gvp promoters, P ( A ) and P ( D ). This sequence is located adjacent to the TATA-box and the transcription factor-B-binding site BRE, suggesting an interaction between GvpE and proteins of the transcription initiation apparatus. Here, we analysed the interaction of GvpE with the five different TATA-box-binding proteins, TBP, of Hbt. salinarum PHH1. The His-tagged TbpA through TbpE proteins were produced in Escherichia coli, bound to Ni-NTA matrices and tested for interaction with GvpE by protein-protein affinity chromatography. All Tbp(His) proteins retained the two different GvpE proteins from lysates of Haloferax volcanii transformants expressing the respective gvpE reading frame in pJAS35. Also, both GvpE(His) proteins bound to Ni-NTA matrices retained TbpB, whereas the 20-kDa soluble gas vesicle protein GvpH(His) neither bound TbpB nor GvpE from the respective lysates of Hfx. volcanii. From these results, it appears that GvpE interacts with any TBP of Hbt. salinarum. This interaction might attract TBP and subsequently TFB and RNAP to the promoter and thus enhance transcription of the gvp gene cluster.
 ...
PMID:Interaction of transcription activator GvpE with TATA-box-binding proteins of Halobacterium salinarum. 2004 18

ZFPs (Zinc Finger Proteins) play important roles in various cellular functions, including transcriptional activation, transcriptional repression, cell proliferation, and development. C(2)H(2) (Cys-Cys-His-His motif) ZFPs are the most abundant proteins among the founding members of the ZFP super family in eukaryotes. In this study, we isolate a novel C(2)H(2) ZNF (Zinc Finger) gene ZNFD. It contains an ORF (Open Reading Frame) with a length of 990 bp, encoding 329 amino acids. The predicted protein contains a C(2)H(2) zinc finger. RT-PCR analysis in 18 human adult tissues indicated that it was expressed in five human adult tissues. Green fluorescence protein localization analysis showed that human ZNFD was located in the nucleus of Hela cells. Overexpression of ZNFD in the COS7 cells activates the transcriptional activities of AP1(PMA) (Activator of protein 1, that responds specifically to phorbol ester). Together the data indicate that ZNFD is probably a new type of C(2)H(2) ZFP and the ZNFD protein may act as a transcriptional activator in PKC (protein kinase C) signal pathway to mediate cellular functions.
 ...
PMID:Isolation and characterization of a novel zinc finger gene, ZNFD, activating AP1(PMA) transcriptional activities. 2016 41

Many bacteria transport mannitol via the mtlAF-encoded phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS). In most firmicutes the transcriptional activator MtlR controls expression of the mtl operon. MtlR possesses an N-terminal DNA binding domain, two PTS regulation domains (PRDs), an EIIB(Gat)- and EIIA(Mtl)-like domain. These four regulatory domains contain one or two potential PTS phosphorylation sites. Replacement of His-342 or His-399 in PRD2 with Ala prevented the phosphorylation of Bacillus subtilis MtlR by PEP, EI and HPr. These mutations as well as EI inactivation caused a loss of MtlR function in vivo. In contrast, phosphomimetic replacement of His-342 with Asp rendered MtlR constitutively active. The absence of phosphorylation in PRD2 serves as catabolite repression mechanism. When EIIA(Mtl) and the soluble EIIB(Mtl) domain of the EIICB(Mtl) permease were included in the phosphorylation mixture, His-599 in the EIIA-like domain of MtlR also became phosphorylated. Replacement of His-599 with Asp rendered MtlR inactive, while His599Ala replacement caused slightly constitutive, glucose-repressible MtlR activity. Doubly mutated His342Ala/His599Ala MtlR was still phosphorylated by EI, HPr and EIIA(Mtl) at Cys-419 in the EIIB(Gat)-like domain. Cys419Ala replacement and deletion of EIIA(Mtl) caused strong constitutive glucose-repressible MtlR activity. This is the first report that Cys phosphorylation controls PRD-containing transcriptional activators.
 ...
PMID:Control of Bacillus subtilis mtl operon expression by complex phosphorylation-dependent regulation of the transcriptional activator MtlR. 2044 94

Two almost identical gene clusters, tphR(I)C(I)A2(I)A3(I)B(I)A1(I) and tphR(II)C(II)A2(II)A3(II)B(II)A1(II), are responsible for the conversion of terephthalate (TPA) to protocatechuate in Comamonas sp. strain E6. In the present study, we investigated the transcriptional regulation of the tphR(II)C(II)A2(II)A3(II)B(II)A1(II) gene cluster. Reverse transcription-PCR analysis suggested that the tphR(II)C(II)A2(II)A3(II)B(II)A1(II) genes form two transcriptional units, the tphC(II)A2(II)A3(II)B(II)A1(II) catabolism operon and tphR(II), with the latter encoding an IclR-type transcriptional regulator (ITTR). The transcription start site of the tph(II) catabolism operon was mapped at 21 nucleotides upstream of the initiation codon of tphC(II). The lacZ transcriptional fusion experiments showed that tphR(II) encodes a transcriptional activator of the tph(II) catabolism operon and that TPA acts as an inducer. On the other hand, TphR(II) appeared to repress its own transcription regardless of the presence of TPA. The analysis of mutant derivatives of E6 indicated that tphR(II) is essential for the transcriptional activation of the tph(II) catabolism operon and the growth on TPA of a tph(I)-deficient derivative of E6. Purified His-tagged TphR(II) bound specifically to the tphR(II)-tphC(II) intergenic region containing a 21-bp inverted repeat sequence. Alignment of the inverted repeat sequences in the binding sites for TphR(II) and other members of ITTRs revealed highly conserved nucleotides. The substitution of conserved nucleotides resulted in significantly reduced TPA-dependent transcriptional activation from the tphC(II) promoter and reduced binding to His-tagged TphR(II). These results clearly indicate that the conserved nucleotides are required for the inducible expression of the tph(II) catabolism operon regulated by TphR(II).
 ...
PMID:Transcriptional regulation of the terephthalate catabolism operon in Comamonas sp. strain E6. 2065 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>