Disease relevance of Bc

• A chromosomal breakage within this cluster explains the current composition of the extended Hox cluster (with Evx, Hox and Mox genes) and the ParaHox cluster [1].

Psychiatry related information on Bc

• Among these we emphasize the identification of proteins with molecular chaperone properties (heat shock proteins and PPIases) and protein spots involved in defense responses such as antioxidant and immunological defense mechanisms (thioredoxin, prophenoloxidase, and serine proteases), as well as in signal transduction pathways [2].

High impact information on Bc

• Clones corresponding to two distinct A1 and A2 chorion genes have been isolated from a cDNA library in Drosophila melanogaster and characterized by hybrid-selected translation and blotting-hybridization analysis [3].
• According to in situ hybridization results, the A1 and A2 genes are not linked (mapping in regions 66D 10-12 and 54C-D of the third and second chromosomes, respectively) [3].
• The E75 A unit is a coextensive with the E75 gene and contains six exons: two 5'-proximal exons, A0 and A1, which are specific to this unit, and exons 2-5, which are common to both units [4].
• The two putative zinc fingers that characterize the DNA-binding domain are encoded by exon A1 and exon 2, so that the E75 A protein contains both fingers, whereas the E75 B protein contains only the second [4].
• Moreover, PGRP-LE activates the prophenoloxidase cascade, a proteolytic cascade in the hemolymph [5].

Biological context of Bc

• Egg-to-adult and relative viabilities in the variants did not decrease at temperature between 18 and 29 degrees C. Genetic analyses indicated that the genes showing the phenotype of variants are new alleles of Mox and Dox-3 on the second chromosome [6].
• Enzyme assays show that Dox-A2 heterozygotes have diphenol oxidase activity reduced to 47-79% of wild type, whereas monophenol oxidase activity, at 94-106% of wild type, is normal [7].
• This inhibitor, M. sexta serpin-3, contains a reactive site loop strikingly similar to the proteolytic activation site in prophenoloxidase (pro-PO) [8].
• Upon activation of the prophenoloxidase activating system in the shrimp, Penaeus monodon, a cell adhesion activity in the haemolymph is generated [9].
• PPAF-I is directly involved in the activation of pro-phenoloxidase (pro-PO) by limited proteolysis and the overall structure is highly similar to that of Drosophila easter serine protease, an essential serine protease zymogen for pattern formation in normal embryonic development [10].

Anatomical context of Bc

• Phenol oxidase exists in Drosophila hemolymph as a prophenol oxidase, A1 and A3, that is activated in vivo with a native activating system, AMM-1, by limited proteolysis with time [11].
• The activation of phenoloxidase and the site-specific localization of the ensuing melanotic response are such critical components of the blood cell response that Spn27A and the signaling elements mediating its activity are likely to represent prime targets for immune suppression by L. boulardi [12].
• Alleles of lz lacking paracrystalline inclusions in their hemocytes do not have phenoloxidase activity whereas alleles with paracrystalline inclusions have enzyme activity [13].
• The deduced protein, however, exhibits extensive similarity (58-81%) to the mouse mast cell tum- antigen, P91A [Lurquin et al., Cell 58 (1989) 293-303] and may identify the normal mouse protein as a DOX [14].
• P91Ap is a constituent of the cytosol; despite a remarkable homology to the Drosophila diphenol oxidase DOX-A2, it separates from murine catechol oxidase activity in rate zonal sedimentation analysis [15].

Associations of Bc with chemical compounds

• Arthropod melanization is controlled by a cascade of serine proteases that ultimately activates the enzyme prophenoloxidase (PPO), which, in turn, catalyzes the synthesis of melanin [16].
• Thus the reversibility of the activation of A1 in response to the change of the concentration of 2-propanol in the activating mixture could be observed [17].
• The two isoforms, A1 and A3, could be separated by ammonium sulfate fractionation [18].
• The prophenoloxidase (proPO) cascade is a major innate immune response in invertebrates, which is triggered into its active form by elicitors, such as lipopolysaccharide, peptidoglycan, and 1,3-beta-D-glucan [19].
• Clones encoding pro-phenol oxidase [pro-PO; zymogen of phenol oxidase (monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1)] A1 were isolated from a lambda gt10 library that originated from Drosophila melanogaster strain Oregon-R male adults [20].

Regulatory relationships of Bc

• In Drosophila, the serpin Spn27A regulates melanization apparently by inhibiting the protease that activates phenoloxidase, the key enzyme in melanin synthesis [21].
• This suggests that the purified 45-kDa Tm-mas is an activated form of pro-PO activating factor [22].

Other interactions of Bc

• The availability of prophenol oxidase cDNA should be useful in revealing the biochemical differences between A1 and A3 isoforms in Drosophila melanogaster that are refractory or unable to activate prophenol oxidase [11].
• The diphenol oxidase activity in double mutant combinations shows that these mutations and Dox-A2 (Pentz et al., 1986) affect this enzyme in different ways [23].
• Furthermore, when Tenebrio hemolymph was incubated with Ca2+ and beta-1,3-glucan, the conversion of pro-PO to PO and the 55-kDa zymogen Tm-mas to the 45-kDa protein, was faster than in the presence of Ca2+ only [22].
• These results suggested that phenoloxidase and tyrosine-3-hydroxylase act as indispensable proteins to maintain life in Drosophila [24].

Analytical, diagnostic and therapeutic context of Bc

• The native states of A1 and A3 are considered to be homodimeric, as judged by gel-filtration chromatography [18].
• The molecular weights of the monomers of A1 and A3 were estimated by SDS-PAGE to be 78 and 77 kDa, respectively [18].

References