Disease relevance of Drs

• Cysteine-rich portions expressed from trx cDNAs in Escherichia coli are capable of zinc binding in vitro, suggesting a possible function for the trx product as a metal-dependent DNA-binding protein [1].
• It contains two ORFs: the 5' ORF is related to the retroviral gag gene and encodes a protein with cysteine-rich motifs that are thought to form a "zinc-knuckle" in a nucleic-acid binding protein; the 3' ORF encodes a putative reverse transcriptase that includes the conserved domains found in reverse transcriptases from other LINEs and retroviruses [2].

Psychiatry related information on Drs

• Evidence is now accumulating that many of the co-factors (E12, Id, MEF2 and CRP proteins) that regulate MRF activity in mammals are also present in lower vertebrates [3].

High impact information on Drs

• wingless, a segment polarity gene required in every segment for the normal development of the Drosophila embryo, encodes a cysteine-rich protein with a signal peptide [4].
• In particular, drosomycin expression, which is regulated by the Toll pathway during the systemic response, is regulated by imd in the respiratory tract, thus demonstrating the existence of distinct regulatory mechanisms for local and systemic induction of antimicrobial peptide genes in Drosophila [5].
• We have examined the requirement of Dorsal and DIF for drosomycin expression in larval fat body cells, the predominant immune-responsive tissue, using the yeast site-specific flp/FRT recombination system to generate cell clones homozygous for a deficiency uncovering both the dorsal and the dif genes [6].
• This result suggests a functional redundancy between both Rel proteins in the control of drosomycin gene expression in the larvae of Drosophila [6].
• This result was independently confirmed by the demonstration that a dominant-negative version of the kinase Pelle can block induction of drosomycin by the cytokine Spaetzle, but does not affect induction of the antibacterial peptide attacin by lipopolysaccharide [7].

Biological context of Drs

• In addition, fon-RNAi larvae exhibit melanotic tumors and constitutive expression of the antifungal peptide gene Drosomycin (Drs), while fon-RNAi pupae display an aberrant pupal phenotype [8].
• Upregulation of genes belonging to the drosomycin family in diapausing adults of Drosophila triauraria [9].
• dUbc9 negatively regulates the Toll-NF-kappa B pathways in larval hematopoiesis and drosomycin activation in Drosophila [10].
• In particular, the molecular characterization of the regulatory pathway controlling the antifungal peptide drosomycin has revealed the importance of Toll receptors in innate immunity [11].
• Six genes, Drs-lC, Drs-lD, Drs-lE, Drs-lF, Drs-lG and Drs-lI, show homology to the Drs form in a multigene family on the 3rd chromosome of D. melanogaster [12].

Anatomical context of Drs

• Here we report the isolation from the hemolymph of immune induced larvae of the lepidopteran Heliothis virescens of a cysteine-rich molecule with exclusive antifungal activity [13].
• Both AeToll1A and AeToll5, like their Drosophila counterparts, activate transcription of drosomycin promoter in both Aedes and Drosophila cell lines [14].
• Cysteine string protein (CSP) is a 34 kDa secretory vesicle protein bearing a "J-domain" as well as a palmitoylated cysteine-rich "string" region used for membrane attachment [15].

Associations of Drs with chemical compounds

• The putative extracellular region contains four tandem repeats of a cysteine-rich motif which is similar to a cysteine pattern present in procollagen and in thrombospondin [16].
• Structure analysis of drosomycin and Rs-AFP2, and comparisons with the other modeled antifungal structures, revealed that the two proteins shared a hydrophobic cluster located at the protein surface in which a lysine residue is embedded [17].

Regulatory relationships of Drs

• In transiently transfected cells, Tehao activated both Dorsal and the transcription of endogenous drosomycin and metchnikowin genes [18].

Other interactions of Drs

• However, the similarities between drosomycin-like in D. triauraria and the members of the drosomycin family in D. melanogaster are quite lower than those between other homologous genes in these species [9].
• Expression of the gene encoding the antifungal peptide Drosomycin in Drosophila adults is controlled by the Toll signaling pathway [6].
• Interestingly, DaPKC functions downstream of the nuclear translocation of Dorsal or Dif, controlling the transcriptional activity of the Drosomycin promoter [19].
• The Toll-9 gene is expressed in adult and larval stages prior to microbial challenge, and the expression correlates with the high constitutive level of drosomycin mRNA in the animals [20].
• We also report that, in contrast to the antibacterial peptides, the antifungal peptide drosomycin remains inducible in a homozygous imd mutant background [21].

Analytical, diagnostic and therapeutic context of Drs

• Molecular cloning revealed that plexus encodes a novel 1990-amino acid protein with cysteine-rich motifs [22].
• We also used site-directed mutagenesis to determine the importance of the MSL-2 RING finger domain and second cysteine-rich motif [23].
• Mass spectrometry and circular dichroism spectroscopy analysis revealed that the recombinant peptide has identical molecular weight and correct structural conformation to native Drosomycin [24].
• The fusion Drosomycin protein with a carrier of Glutathione S-transferase (GST) was initially purified by affinity chromatography followed by Enterokinase cleavage [24].

References