Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cg30 gene of Autographa californica nuclear polyhedrosis virus (AcMNPV) encodes two sequence motifs, a zinc finger-like motif and a leucine zipper, found in other polypeptides known to be involved in gene regulation. To gain insight into the function of the cg30 product, CG30, we constructed and characterized recombinant viruses lacking a functional cg30 gene. We found that cg30 mutants had no striking phenotype in cell lines derived from Spodoptera frugiperda or Trichoplusia ni or in T. ni larvae. Although cg30 is known to be transcribed as an early monocistronic RNA and as the second cistron of an abundant late bicistronic RNA, production of a CG30-beta-galactosidase fusion protein was observed mainly at early times postinfection. Viruses containing cg30 had a subtle growth advantage over those lacking cg30 after several viral passages in cell culture. We employed transient expression assays to determine whether cg30 and pe-38, an AcMNPV gene that encodes a polypeptide with zinc finger-like and leucine zipper motifs similar to those of cg30, have redundant functions. Although pe-38 may have a role in AcMNPV gene expression, there was no indication that cg30 and pe-38 are functionally redundant.
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PMID:In vivo and in vitro analyses of recombinant baculoviruses lacking a functional cg30 gene. 828 48

Egr-1 is an immediate-early response gene induced transiently and ubiquitously by mitogenic stimuli and also regulated in response to signals that initiate differentiation. The Egr-1 gene product, a nuclear phosphoprotein with three zinc fingers of the Cys2His2 class, binds to the sequence CGCCCCCGC and transactivates a synthetic promoter construct 10-fold in transient-transfection assays. We have analyzed the structure and function of the Egr-1 protein in detail, delineating independent and modular activation, repression, DNA-binding, and nuclear localization activities. Deletion analysis, as well as fusions to the DNA-binding domain of GAL4, indicated that the activation potential of Egr-1 is distributed over an extensive serine/threonine-rich N-terminal domain. In addition, a novel negative regulatory function has been precisely mapped 5' of the zinc fingers: amino acids 281 to 314 are sufficient to confer the ability to repress transcription on a heterologous DNA-binding domain. Specific DNA-binding activity was shown to reside in the three zinc fingers of Egr-1, as predicted by homology to other known DNA-binding proteins. Finally, nuclear localization of Egr-1 is specified by signals in the DNA-binding domain and basic flanking sequences, as determined by subcellular fractionation and indirect immunofluorescence. Basic residues 315 to 330 confer partial nuclear localization on the bacterial protein beta-galactosidase. A bipartite signal consisting of this basic region in conjunction with either the second or third zinc finger, but not the first, suffices to target beta-galactosidase exclusively to the nucleus. Our work shows that Egr-1 is a functionally complex protein and suggests that it may play different roles in the diverse settings in which it is induced.
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PMID:A novel repression module, an extensive activation domain, and a bipartite nuclear localization signal defined in the immediate-early transcription factor Egr-1. 833 1

Insertional mutagenesis using P-element vectors yielded several independent mutations that cause male homosexuality in Drosophila melanogaster. Subsequent analyses revealed that all of these insertions were located at the same chromosomal division, 91B, where one of the inversion breakpoints responsible for the bisexual phenotype of the fruitless (fru) mutant has been mapped. In addition to the altered sexual orientation, the fru mutants displayed a range of defects in the formation of a male-specific muscle, the muscle of Lawrence. Since the male-specific formation of this muscle was dependent solely on the sex of the innervating nerve and not on the sex of the muscle itself, the primary site of action of the fru gene should be in the neural cells. satori, one of the P-insertion alleles of fru which we isolated, carried the lacZ gene of E. coli as a reporter, and beta-galactosidase expression was found in a subset of brain cells including those in the antennal lobe in the satori mutant. Targeted expression of a sex determination gene, transformer (tra), was used to produce chromosomally male flies with certain feminized glomeruli in the antennal lobe. Such sexually mosaic flies courted not only females but also males when the DM2, DA3 and DA4 glomeruli were feminized, indicating that these substructures in the antennal lobe may be involved in the determination of the sexual orientation of flies. Molecular cloning and analyses of the genomic and complementary DNAs indicated that transcription of the fru locus yields several different transcripts, one of which encodes a putative transcription regulator with a BTB domain and two zinc finger motifs. In the 5' non-coding region, three putative Transformer binding sites were identified. It appears plausible therefore that the fru gene is one of the elements in the sex determination cascade that controls sexual fates of certain neuronal cells. Improper sex determination in these neural cells may lead to altered sexual orientation and malformation of the male-specific muscle. Some implications of the results of our study on sexual orientation in other organisms will be discussed based on the Drosophila research.
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PMID:Genetic dissection of sexual orientation: behavioral, cellular, and molecular approaches in Drosophila melanogaster. 895 72

GLI is the prototype for the Gli-Kruppel gene family characterized by a consensus C2-H2 zinc finger domain and is believed to function as a transcription activator in the vertebrate Sonic hedgehog-Patched signal transduction pathway. Understanding GLI gene regulation may be of importance to understanding causes of human birth defects and cancer. To begin to understand the regulation of this developmentally important gene we have cloned the human GLI gene and functionally characterized its 5' flanking region. The GLI gene is composed of 12 exons and 11 introns and in the zinc finger coding region shares a highly conserved splicing pattern with several other Gli family members in both vertebrates and C. elegans. A major transcription initiation site was identified upstream of the GLI translation start site along with three minor transcription initiation sites. The region surrounding the transcription initiation sites lacks TATA and CCAAT consensus sequences, has a high GC content, includes a CpG island, and contains several GC boxes. A 487bp segment surrounding the transcription initiation sites increased expression of a luciferase reporter gene 15-fold in Tera-1 cells and was defined as the core promoter region of human GLI. In transgenic mice this region directed beta-galactosidase expression to the central nervous system on embryonic days 10.5-12.5 and to sites of endochondral ossification on embryonic days 12.5 and 13.5 in a pattern comparable to the endogenous expression pattern of mouse gli within these tissues. The previously identified gastrointestinal expression of gli was not driven by this region and may require elements outside of the core promoter. Sequence analysis of the 5' flanking region of the mouse gli gene and the full-length mouse gli cDNA demonstrated high homology with human GLI, suggesting conservation of GLI regulation and function.
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PMID:Characterization of the promoter region and genomic organization of GLI, a member of the Sonic hedgehog-Patched signaling pathway. 952 1

The assembly pathway of spliceosomal snRNPs in yeast is poorly understood. We devised a screen to identify mutations blocking the assembly of newly synthesized U4 snRNA into a functional snRNP. Fifteen mutant strains failing either to accumulate the newly synthesized U4 snRNA or to assemble a U4/U6 particle were identified and categorized into 13 complementation groups. Thirteen previously identified splicing-defective prp mutants were also assayed for U4 snRNP assembly defects. Mutations in the U4/U6 snRNP components Prp3p, Prp4p, and Prp24p led to disassembly of the U4/U6 snRNP particle and degradation of the U6 snRNA, while prp17-1 and prp19-1 strains accumulated free U4 and U6 snRNA. A detailed analysis of a newly identified mutant, the sad1-1 mutant, is presented. In addition to having the snRNP assembly defect, the sad1-1 mutant is severely impaired in splicing at the restrictive temperature: the RP29 pre-mRNA strongly accumulates and splicing-dependent production of beta-galactosidase from reporter constructs is abolished, while extracts prepared from sad1-1 strains fail to splice pre-mRNA substrates in vitro. The sad1-1 mutant is the only splicing-defective mutant analyzed whose mutation preferentially affects assembly of newly synthesized U4 snRNA into the U4/U6 particle. SAD1 encodes a novel protein of 52 kDa which is essential for cell viability. Sad1p localizes to the nucleus and is not stably associated with any of the U snRNAs. Sad1p contains a putative zinc finger and is phylogenetically highly conserved, with homologues identified in human, Caenorhabditis elegans, Arabidospis, and Drosophila.
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PMID:A novel genetic screen for snRNP assembly factors in yeast identifies a conserved protein, Sad1p, also required for pre-mRNA splicing. 1002 88

The zinc finger transcription factors GATA4, -5, and -6 and the homeodomain protein Nkx2.5 are expressed in the developing heart and have been shown to activate a variety of cardiac-specific genes. To begin to define the regulatory relationships between these cardiac transcription factors and to understand the mechanisms that control their expression during cardiogenesis, we analyzed the mouse GATA6 gene for regulatory elements sufficient to direct cardiac expression during embryogenesis. Using beta-galactosidase fusion constructs in transgenic mice, a 4.3-kb 5' regulatory region that directed transcription specifically in the cardiac lineage, beginning at the cardiac crescent stage, was identified. Thereafter, transgene expression became compartmentalized to the outflow tract, a portion of the right ventricle, and a limited region of the common atrial chamber of the embryonic heart. Further dissection of this regulatory region identified a 1.8-kb cardiac-specific enhancer that recapitulated the expression pattern of the larger region when fused to a heterologous promoter and a smaller 500-bp subregion that retained cardiac expression, but was quantitatively weaker. The GATA6 cardiac enhancer contained a binding site for Nkx2.5 that was essential for cardiac-specific expression in transgenic mice. These studies demonstrate that GATA6 is a direct target gene for Nkx2.5 in the developing heart and reveal a mutually reinforcing regulatory network of Nkx2.5 and GATA transcription factors during cardiogenesis.
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PMID:Direct activation of a GATA6 cardiac enhancer by Nkx2.5: evidence for a reinforcing regulatory network of Nkx2.5 and GATA transcription factors in the developing heart. 1062 55

The Aspergillus nidulans zinc finger transcription factor PacC is activated by proteolytic processing in response to ambient alkaline pH. The pH-regulated step is the transition of full-length PacC from a closed to an open, protease-accessible conformation. Here we show that in the absence of ambient pH signaling, the C-terminal negative-acting domain prevents the nuclear localization of full-length closed PacC. In contrast, the processed PacC form is almost exclusively nuclear at any ambient pH. In the presence of ambient pH signaling, the fraction of PacC that is in the open conformation but has not yet been processed localizes to the nucleus. Therefore, ambient alkaline pH leads to an increase in nuclear PacC by promoting the proteolytic elimination of the negative-acting domain to yield the processed form and by increasing the proportion of full-length protein that is in the open conformation. These findings explain why mutations resulting in commitment of PacC to processing irrespective of ambient pH lead to permanent PacC activation and alkalinity mimicry. A nuclear import signal that targets Escherichia coli beta-galactosidase to the nucleus has been located to the PacC zinc finger region. A mutation abolishing DNA binding does not prevent nuclear localization of the processed form, showing that PacC processing does not lead to nuclear localization by passive diffusion of the protein made possible by the reduction in size, followed by retention in the nucleus after DNA binding.
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PMID:Ambient pH signaling regulates nuclear localization of the Aspergillus nidulans PacC transcription factor. 1123 6

The activation of the pleomorphic adenoma gene 1 (PLAG1) is the most frequent gain-of-function mutation found in pleomorphic adenomas of the salivary glands. To gain more insight into the regulation of PLAG1 function, we searched for PLAG1-interacting proteins. Using the yeast two-hybrid system, we identified karyopherin alpha2 as a PLAG1-interacting protein. Physical interaction between PLAG1 and karyopherin alpha2 was confirmed by an in vitro glutathione S-transferase pull-down assay. Karyopherin alpha2 escorts proteins into the nucleus via interaction with a nuclear localization sequence (NLS) composed of short stretches of basic amino acids. Two putative NLSs were identified in PLAG1. The predicted NLS1 (KRKR) was essential for physical interaction with karyopherin alpha2 in glutathione S-transferase pull-down assay, and its mutation resulted in decreased nuclear import of PLAG1. Moreover, NLS1 was able to drive the nuclear import of the cytoplasmic protein beta-galactosidase. In contrast, predicted NLS2 of PLAG1 (KPRK) was not involved in karyopherin alpha2 binding nor in its nuclear import. The residual nuclear import of PLAG1 after mutation of the NLS1 was assigned to the zinc finger domain of PLAG1. These observations indicate that the nuclear import of PLAG1 is governed by its zinc finger domain and by NLS1, a karyopherin alpha2 recognition site.
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PMID:Identification of a karyopherin alpha 2 recognition site in PLAG1, which functions as a nuclear localization signal. 1188 54

In eukaryotic cells, intracellular proteolysis occurs mainly via the ubiquitin-proteasome system. Expression of the yeast proteasome is under the control of the transcription factor, Rpn4p (also known as Son1p/Ufd5p). We show here that the RPN4 gene promoter contains regulatory sequences that bind Pdr1p and Pdr3p, two homologous zinc finger-containing transcription factors, which mediate multiple drug resistance through the expression of membrane transporter proteins. Mutations in the RPN4 Pdr1p/Pdr3p binding sites lead to decreased expression of the proteasome RPT6 gene and to defective ubiquitin-mediated proteolysis. Pdr3p, but not Pdr1p, is required for normal levels of intracellular proteolysis, indicating that the two transcription factors have distinct functions in the control of RPN4 expression. The RPN4 promoter contains an additional sequence that binds Yap1p, a bZIP-type transcription factor that plays an important role in the oxidative stress response and multidrug resistance. We also show that the Yap1p response element is important in the transactivation of RPN4 by Yap1p. In yeast cells lacking Pdr1p, ubiquitin-Pro-beta-galactosidase, a short-lived protein used to assay proteasome activity, is stabilized by the loss of Yap1p. These data demonstrate that the ubiquitin-proteasome system is controlled by transcriptional regulators of multidrug resistance via RPN4 expression.
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PMID:Control of 26S proteasome expression by transcription factors regulating multidrug resistance in Saccharomyces cerevisiae. 1191 14

The vertebrate Slug gene encodes a zinc finger-containing transcriptional repressor. Here we report expression of the mouse Slug gene during organogenesis and late fetal development using histochemical detection of beta-galactosidase expressed from a targeted Slug(lacZ) knock-in allele. The Slug gene is highly expressed in the mesenchymal or stromal component of numerous organs. It is also highly expressed in craniofacial mesenchyme, in bone of both mesodermal and neural crest origin, and in the outflow tract and the endocardial cushions of the heart.
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PMID:Slug expression during organogenesis in mice. 1255 34


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