Disease relevance of LAP3

• The mammalian BLM hydrolase is a cysteine protease that inactivates BLM to relieve the toxicity of BLM to normal and tumor cells [1].
• Although the lysosomal cysteine proteinase cathepsin B is alkaline pH-labile, active, stable high molecular mass forms have been reported previously from the culture medium of human and murine mammary tumor explants and the sputum of patients with purulent bronchiectasis [2].
• In this study, the yeast bleomycin hydrolase gene was expressed in Escherichia coli, and site-directed mutagenesis was employed to precisely investigate the roles of the conserved Cys102 and His398 residues in its structure and enzymatic activity [3].
• Gene cloning and characterization of PepC, a cysteine aminopeptidase from Streptococcus thermophilus, with sequence similarity to the eucaryotic bleomycin hydrolase [4].
• Short report: Immunodiagnosis of human fascioliasis using recombinant Fasciola hepatica cathepsin L1 cysteine proteinase [5].

High impact information on LAP3

• The Gal6 protease is in a class of cysteine peptidases identified by their ability to inactivate the anti-cancer drug bleomycin [6].
• In Gal6 the C termini lie in the active site clefts [6].
• The substrate specificity of the peptidase activity is determined by the position of the C terminus of Gal6 rather than the sequence of the substrate [6].
• The homolog in yeast, Gal6, has recently been identified and found to bind DNA and to act as a repressor in the Gal4 regulatory system [7].
• Bleomycin hydrolase is a cysteine protease that hydrolyzes the anticancer drug bleomycin [7].

Chemical compound and disease context of LAP3

• Variant Gal6 proteins that fail to bind nucleic acid also exhibit reduced ability to protect cells from bleomycin toxicity, suggesting that the nucleic acid binding activity of Gal6p is important in bleomycin detoxification and may be involved in its normal biological functions [8].
• Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolase [9].

Biological context of LAP3

• Furthermore, this regulation is conveyed by a binding site for the Gal4 regulatory protein in its promoter, prompting the designation of this gene as GAL6 [10].
• The deduced amino acid sequence (483 amino acids) exhibits surprisingly high homology to vertebrate bleomycin hydrolase (43% identical residues and 22% conserved exchanges) [11].
• Deletion of GAL6 was shown to have a major impact on biomass and ethanol formation when cells were grown on galactose, and from the data obtained we speculate that Gal6 may be involved in mRNA degradation of the GAL gene transcripts [12].
• The open reading frame of BLH1 consists of 1,449 base pairs encoding a 55.4-kDa protein consistent with the molecular mass found in sodium dodecyl sulfate-polyacrylamide gel electrophoresis [13].
• Transfection of ycp1 into NIH 3T3 cells induced resistance of these cells to BLM [14].

Anatomical context of LAP3

• The results demonstrate that increased BLM hydrolase activity in NIH 3T3 cells causes BLM resistance and that inhibition of BLM metabolism sensitizes these cells to BLM [14].
• Part of Blh1p is associated with plasma membranes, and most of the rest occurs in the cytosol [15].
• PPV were gradually acidified and matured by fusion with lysosomes containing a digestive hydrolase, cysteine proteinase, and a membrane-permeabilizing peptide amoebapore [16].
• Cystatin, a superfamily of cysteine proteinase inhibitor of cathepsins and other cysteine proteinases, is widely distributed in animal tissues and body fluids [17].

Associations of LAP3 with chemical compounds

• Bleomycin hydrolase is a cysteine peptidase discovered through its ability to detoxify the anti-cancer glycopeptide, bleomycin [10].
• The cysteine-peptidase bleomycin hydrolase is a member of the galactose regulon in yeast [10].
• Yeast bleomycin hydrolase is a DNA-binding cysteine protease. Identification, purification, biochemical characterization [1].
• The Gal6 channel is lined with 60 lysine residues from the six subunits, suggesting a role in DNA binding [7].
• The ycp1-induced BLM resistance was completely reversed by the cysteine proteinase inhibitor E-64, a known inhibitor of BLM hydrolase [14].

Other interactions of LAP3

• The GAL6 deletion does not affect the expression of another inducible gene, HSP26 [10].
• The results suggest a major role of Imp2 in a GAL6-independent pathway [18].
• The role of the proteins encoded by the GAL80 gene, the MIG1 gene and the GAL6 gene in glucose control of galactose consumption by Saccharomyces cerevisiae was studied by physiological characterisation of various GAL mutant strains [12].

Analytical, diagnostic and therapeutic context of LAP3

• The normal physiological function of BLM hydrolase is not known, but its activity limits the use of BLM in cancer chemotherapy [1].
• Using protein sequence-derived degenerate oligonucleotide primers and amplification by polymerase chain reaction, the yeast gene BLH1 was isolated and characterized [11].
• A method for a 50-60-fold purification of a cysteine proteinase from trophozoites of Entamoeba histolytica using 35-80% ammonium sulphate fractionation, gel chromatography on Sephadex G-75, and preparative isoelectric focusing is described [19].
• First, the partial cysteine proteinase gene from C. sinensis was cloned by performing reverse transcription polymerase chain reaction (RT-PCR) with degenerate oligonucleotide primers derived from conserved cysteine proteinase sequences [20].

References