Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An examination of the DNA binding domain structure of bovine plasma fibronectin (Fn) was undertaken by a combination of limited proteolytic cleavage and Western blotting. A time course digestion of fibronectin with cathepsin D produced a number of proteolytic fragments possessing DNA binding activity. After two min digestion, two DNA binding fibronectin fragments of Mr approximately 180kd and 120kd were detected. Upon further digestion, a fibronectin fragment of Mr 18kd was detected. Thus it would appear that under physiological ionic strength only a single DNA binding domain exists in the fibronectin molecule. It was also demonstrated that the interaction of fibronectin with DNA is not ionic in nature, as heat denaturation of protein totally abolishes the DNA binding activity. An examination of possible sequence specificity of DNA binding activity of fibronectin was also undertaken by dot blotting the bovine plasma fibronectin and using [32P] labelled lambda FC 40 DNA containing approximately 16 kd of 5' end of the chicken fibronectin gene. Its binding to fibronectin was approximately twice the binding of [32P] labelled wild type lambda, where as binding to control of equimolar concentration of calf thymus histone H 2 A was approximately equal. The use of a smaller subcloned region, a approximately 1.9kb fragment of DNA from the 5' end of chicken fibronectin gene and wild type lambda DNA showed approximately 2 fold increase in histone binding and approximately 7 fold increase in fibronectin binding, indicating preferential fibronectin binding with eukaryotic DNA as compared to prokaryotic DNA. Further investigation of sequence specificity showed that a 0.45kb DNA fragment from the 5' end of chicken fibronectin gene, containing a number of elements characteristic of promoter, demonstrated approximately 2 fold higher level of binding with fibronectin and approximately 3.5 fold less binding activity with equimolar concentration of histone H2A when compared with a 1.4kb fragment of chicken fibronectin gene from the 1st exon. These results suggest fibronectin binding may be preferential to the promoter region of its own gene which could have possibly a regulatory function.
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PMID:The interaction between fibronectin and DNA. 275 Dec 62

Hydrolysis of histones by proteinases from rat liver, skin and other sources was studied by using a rat thymus histone preparation as the substrate and polyacrylamide-gel electrophoresis and densitometric analysis as the methods to detect histone subtypes and their hydrolysis. The rat mast-cell proteinase I effectively hydrolysed histones except type H4. Thrombin hydrolysed effectively histones H1 and H2A, whereas plasmin hydrolysed all types of histones. Cathepsin D hydrolysed especially histone H2A. Cathepsins B and L hydrolysed all histones more slowly, and cathepsin H hydrolysed them extremely slowly. Epidermal aminoendopeptidase did not hydrolyse histones. Trypsin and chymotrypsin were used as reference enzymes, which hydrolysed all types of histones in very low concentrations. This study suggests that a variety of proteinases could play a role in histone hydrolysis. Hydrolysis of a specific subtype of histones, such as histone H2A at pH 6 by cathepsin D, may be directly involved in regulation of epidermal-cell differentiation.
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PMID:Hydrolysis of histones by proteinases. 296 88

Parasin I is a potent 19-residue antimicrobial peptide isolated from the skin mucus of wounded catfish (Parasilurus asotus). Here we describe the mechanism of parasin I production from histone H2A in catfish skin mucosa on epidermal injury. Cathepsin D is found to exist in the mucus as an inactive proenzyme (procathepsin D), and a metalloprotease, induced on injury, cleaves procathepsin D to generate active cathepsin D. This activated form of cathepsin D then cleaves the Ser19-Arg20 bond of histone H2A to produce parasin I. Immunohistochemical analysis reveals that unacetylated histone H2A, a precursor of parasin I, and procathepsin D are present in the cytoplasm of epithelial mucous cells and that parasin I is produced on the mucosal surface on epidermal injury. Western blot analysis shows that parasin I is also present in the skin mucus of other fish species. Furthermore, parasin I shows good antimicrobial activity against fish-specific bacterial pathogens. Taken together, these results indicate that cathepsin D and a metalloprotease participate in the production of parasin I from histone H2A and that parasin I contributes to the innate host defense of the fish against invading microorganisms.
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PMID:Cathepsin D produces antimicrobial peptide parasin I from histone H2A in the skin mucosa of fish. 1182 Dec 59

A 19-residue antimicrobial peptide parasin I is generated from histone H2A in the skin mucus of catfish by the action of cathepsin D activated by a procathepsin D-processing enzyme induced upon epidermal injury. Here we report the isolation and characterization of the procathepsin D-processing enzyme in the mucus of wounded catfish. Sequence analysis of the cDNA identified the purified procathepsin D-processing enzyme as matrix metalloproteinase 2 (MMP 2). By acting as a procathepsin D convertase upon epidermal injury, MMP 2 is involved in the regulation of parasin I production in catfish skin mucosa.
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PMID:Matrix metalloproteinase 2 is involved in the regulation of the antimicrobial peptide parasin I production in catfish skin mucosa. 1243 93

A novel recombinant protein tetra-H2A (TH) derived from histone H2A has been developed to replace protamine as a conditionally reversible, nucleic acid condensing agent. The novel protein will address the insufficient release of nucleic acid therapeutics, which is captured by protamine for siRNA delivery. TH is composed of 4 tandem repeats of the histone H2A N-terminal sequence, intervened by the cathepsin D cleavage site. The repeating H2A sequence enhances the binding affinity to anionic nucleic acids, forming more stable condensates, as demonstrated by the binding affinity assay. The TH/siRNA condensates are formulated into a core-membrane structured liposomal nanoparticle (NP). The endosomes of cancer cells are rich in cathepsin D, allowing on-site degradation of TH and facilitating the intracellular release of siRNA. The NPs assembled with TH produced a higher silencing efficiency of target genes in vitro and in vivo than the NPs assembled with protamine as the nucleic acid condensing agent. The exploitation of TH in the NP formulation exhibited a biocompatibility profile similar to that of protamine, with minimal immunostimulating and systemic toxicity observed after repeated administration.
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PMID:Incorporation of histone derived recombinant protein for enhanced disassembly of core-membrane structured liposomal nanoparticles for efficient siRNA delivery. 2397 82