Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two proteolytic enzymes, protease A and protease B, were isolated in homogeneous state from the cultural broth of the thermophilic actinomycete Micromonospora vulgaris 42. Their physicochemical properties were studied, i.e., molecular weight (50 000 for protease A and 30 000 for protease B), amino acid composition, N-terminal amino acids (phenylalanine for protease A and alanine for protease B). The specificity of the action of these enzymes was assayed by splitting the B chain of oxidized insulin. Both enzymes are neutral proteases of the thermolysine type.
 ...
PMID:Properties of proteolytic enzymes isolated from a thermophilic strain of Micromonospora vulgaris 42. 0 42

Protease A is 870-fold purified by means of isoelectric precipitation, DEAE-cellulose chromatography and gel filtration through Sephadex G-50, the yield of the enzyme being 28%. The purified preparation is free of contaminant proteolytic activity and is almost homogenous chromatographically, but it produces a complex pattern under electrophoresis in 30% polyacrylamide gel, which is probably due to enzyme autolysis. As evidenced from the effect of protease A on A and B chains of insulin, the enzyme has a wide substrate specificity. It hydrolyses native vetch legumin and vicilin up to peptides having on average 9 and 16 amino acid residues respectively. No free amino acids were found in hydrolysates of both vetch proteins. Thus, protease A is an endopeptidase, which probably plays the main role in the process of reserve proteins degradation.
 ...
PMID:[Partial purification and characterization of protease A of germinating vetch seeds, hydrolyzing native reserve proteins]. 58 33

The pancreatic beta-cell-specific expression of the insulin gene is mediated, at least in part, by the interaction of unique trans-acting beta-cell factors with a cis-acting DNA element found within the insulin enhancer (5'-GC CATCTG-3'; referred to as the insulin control element [ICE]) present in the rat insulin II gene between positions -100 and -91. This sequence element contains the consensus binding site for a group of DNA-binding transcription factors called basic helix-loop-helix proteins (B-HLH). As a consequence of the similarity of the ICE with the DNA sequence motif associated with the cis-acting elements of the B-HLH class of binding proteins (CANNTG), the ability of this class of proteins to regulate cell-type-specific expression of the insulin gene was addressed. Cotransfection experiments indicated that overexpression of Id, a negative regulator of B-HLH protein function, inhibits ICE-mediated activity. Antibody to the E12/E47 B-HLH proteins attenuated the formation, in vitro, of a previously described (J. Whelan, S. R. Cordle, E. Henderson, P. A. Weil, and R. Stein, Mol. Cell. Biol. 10:1564-1572, 1990) beta-cell-specific activator factor(s)-ICE DNA complex. Both of these B-HLH proteins (E12 and E47) bound efficiently and specifically to the ICE sequences. The role of B-HLH proteins in mediating pancreatic beta-cell-specific transcription of the insulin gene is discussed.
 ...
PMID:Pancreatic beta-cell-type-specific transcription of the insulin gene is mediated by basic helix-loop-helix DNA-binding proteins. 199 19

Selective transcription of the insulin gene in pancreatic beta cells is regulated by its enhancer, located between nucleotides -340 and -91 relative to the transcription start site. Transcription from the enhancer is controlled by both positive- and negative-acting cellular factors. Cell-type-specific expression is mediated principally by a single cis-acting enhancer element located between -100 and -91 in the rat insulin II gene (referred to as the insulin control element [ICE]), which is acted upon by both of these cellular activities. Analysis of the effect of 5' deletions within the insulin enhancer has identified a region between nucleotides -217 and -197 that is also a site of negative control. Deletion of these sequences from the 5' end of the enhancer leads to transcription of the enhancer in non-insulin-producing cells, even though the ICE is intact. Derepression of this ICE-mediated effect was shown to be due to the binding of a ubiquitously distributed cellular factor to a sequence element which resides just upstream of the ICE (i.e., between nucleotides -110 and -100). We discuss the possible relationship of these results to cell-type-specific regulation of the insulin gene.
 ...
PMID:Insulin gene expression in nonexpressing cells appears to be regulated by multiple distinct negative-acting control elements. 201 82

The insulin gene is expressed almost exclusively in pancreatic beta-cells. Previous work in our laboratory has shown that pancreatic beta-cell-specific expression of the rat insulin II gene is controlled by a number of positive and negative cis-acting DNA elements within the enhancer. We have shown that one element within the enhancer, located between nucleotides -100 and -91 (GCCATCTGCT; referred to as the insulin control element [ICE]) relative to the transcription start site, is controlled by both positive- and negative-acting cellular transcription factors. The positive-acting factor appears to be uniquely active in beta-cells. To identify the nucleotides within the ICE that mediate positive cell-type-specific regulation, point mutations within this element were generated and assayed for their effects on expression. Base pairs -97, -94, -93, and -92 were found to be crucial for the activator function of this region, while mutations at base pairs -100, -96, and -91 had little or no effect on activity. The gel mobility shift assay was used to determine whether specific cellular factors associated directly with the ICE. Several specific protein-DNA complexes were detected in extracts prepared from insulin-producing and non-insulin-producing cells, including a complex unique to beta-cell extracts. The ability of unlabeled wild-type and point mutant versions of the ICE to compete for binding to these cellular factors demonstrated that the beta-cell-specific complex appears to contain the insulin gene activator protein(s). Interestingly, the adenovirus type 2 major late promoter upstream element (USE; GCCACGTGAC) also competed in the gel mobility shift assay for binding of cellular proteins to the ICE. These results suggested that the cellular factor that binds to the USE (i.e., USF) also interacts with the ICE. This was directly demonstrated by showing that ICE and USE sequences completed for the USF required for adenovirus type 2 major late promoter transcription in vitro and by showing that reticulocyte lysate-translated human USF products bound to the ICE. However, the USE sequences were unable to stimulate beta-cell-type-specific activity in vivo. We discuss the possible relationship of these observations to positive and negative control mediated by the ICE.
 ...
PMID:Identification of a pancreatic beta-cell insulin gene transcription factor that binds to and appears to activate cell-type-specific expression: its possible relationship to other cellular factors that bind to a common insulin gene sequence. 218 Dec 78

In the course of examining the turnover of enzymes and proteins subject to catabolite inhibition and/or catabolite repression in Escherichia coli, we have observed at least three novel calcium- or manganese-activated proteolytic activities restricted to the periplasmic space. The occurrence and level of these proteolytic activities vary with the stage of cell growth and carbon source. Each of these proteases are neutral metalloendoproteases capable of degrading test substrates such as casein, insulin, globin, and protamine and appear to be unique when compared with the known periplasmic proteases in E. coli. One of these proteases (designated protease VII) has been purified to homogeneity and characterized in regard to subunit structure, sensitivity to protease inhibitors and metal ions, and substrate specificity. Immunological and genetic approaches are being employed to determine if these novel proteases arise from a common gene product. The physiological role of these proteases remains to be established.
 ...
PMID:Periplasmic proteases of Escherichia coli. 306 90

Bothrops protease A, an arginine-ester hydrolase, is active on protamine, gelatin and insulin and was isolated from the venom of Bothrops jararaca in a homogeneous state, as judged by polyacrylamide gel electrophoresis and ultracentrifugal analyses. The enzyme has a molecular weight of 65,000 and a pI of 3.55. The enzyme is a glycoprotein whose amino acid content corresponds to 55% of the molecular weight.
 ...
PMID:Biophysical properties and amino acid composition of Bothrops protease A, a proteolytic enzyme isolated from the venom of the snake Bothrops jararaca (jararaca). 635 65

The sulfhydryl protease B was isolated from the cotyledons of 8-day old vetch seedlings and purified 1580-fold with a 38% recovery. The preparation obtained proved to be homogeneous by DEAE-cellulose chromatography and polyacrylamide gel electrophoresis. The molecular weight of the enzyme as shown by Na-DS gel electrophoresis is 38 000. Protease B hydrolyzes the peptide bonds involving the carboxyl groups of asparagine in insulin chains A and B. Since protease B fails to attack the native reserve proteins the high molecular weight products of the initial hydrolysis of reserve proteins by the earlier discovered protease A seem to be the most probable substrates of protease B. A considerable part of these substrates is split by protease B to form large peptides. The role of protease B in reserve proteins degradation is discussed.
 ...
PMID:[Purification and partial characterization of protease B from germinating vetch seeds]. 704 13

Selective transcription of the insulin gene in pancreatic beta cells is regulated by its enhancer, located between nucleotides -340 and -91 relative to the transcription start site. One of the principal control elements within the enhancer is found between nucleotides -100 and -91 (GCCATCTGCT, referred to as the insulin control element [ICE]) and is regulated by both positive- and negative-acting transcription factors in the helix-loop-helix (HLH) family. It was previously shown that the c-jun proto-oncogene can repress insulin gene transcription. We have found that c-jun inhibits ICE-stimulated transcription. Inhibition of ICE-directed transcription is mediated by sequences within the carboxy-terminal region of the protein. These c-jun sequences span an activation domain and the basic leucine zipper DNA binding-dimerization region of the protein. Both regions of c-jun are conserved within the other members of the jun family: junB and junD. These proteins also suppress ICE-mediated transcription. The jun proteins do not appear to inhibit insulin gene transcription by binding directly to the ICE. c-jun and junB also block the trans-activation potential of two skeletal muscle-specific HLH proteins, MyoD and myogenin. These results suggests that the jun proteins may be common transcription control factors used in skeletal muscle and pancreatic beta cells to regulate HLH-mediated activity. We discuss the possible significance of these observations to insulin gene transcription in pancreatic beta cells.
 ...
PMID:c-jun inhibits transcriptional activation by the insulin enhancer, and the insulin control element is the target of control. 826 34

The insulin gene is expressed exclusively in pancreatic islet beta cells. The principal regulator of insulin gene transcription in the islet is the concentration of circulating glucose. Previous studies have demonstrated that transcription is regulated by the binding of trans-acting factors to specific cis-acting sequences within the 5'-flanking region of the insulin gene. To identify the cis-acting control elements within the rat insulin II gene that are responsible for regulating glucose-stimulated expression in the beta cell, we analyzed the effect of glucose on the in vivo expression of a series of transfected 5'-flanking deletion mutant constructs. We demonstrate that glucose-induced transcription of the rat insulin II gene is mediated by sequences located between -126 and -91 bp relative to the transcription start site. This region contains two cis-acting elements that are essential for directing pancreatic beta-cell-type-specific expression of the rat insulin II gene, the insulin control element (ICE; -100 to -91 bp) and RIPE3b1 (-115 to -107 bp). The gel mobility shift assay was used to determine whether the formation of the ICE- and RIPE3b1-specific factor-DNA element complexes were affected in glucose-treated beta-cell extracts. We found that RIPE3b1 binding activity was selectively induced by about eightfold. In contrast, binding to other insulin cis-acting element sequences like the ICE and RIPE3a2 (-108 to -99 bp) were unaffected by these conditions. The RIPE3b1 binding complex was shown to be distinct from the glucose-inducible factor that binds to an element located between -227 to -206 bp of the human and rat insulin I genes (D. Melloul, Y. Ben-Neriah, and E. Cerasi, Proc. Natl. Acad. Sci. USA 90:3865-3869, 1993). We have also shown that mannose, a sugar that can be metabolized by the beta cell, mimics the effects of glucose in the in vivo transfection assays and the in vitro RIPE3b1 binding assays. These results suggested that the RIPE3b1 transcription factor is a primary regulator of glucose-mediated transcription of the insulin gene. However, we found that mutations in either the ICE or the RIPE3b1 element reduced glucose-responsive expression from transfected 5'-flanking rat insulin II gene constructs. We therefore conclude that glucose-regulated transcription of the insulin gene is mediated by cis-acting elements required for beta-cell-type-specific expression.
 ...
PMID:Glucose-induced transcription of the insulin gene is mediated by factors required for beta-cell-type-specific expression. 828 26


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