Disease relevance of CecA1

• Cecropin A, the common product of the CecA1 and A2 genes, was identified in the hemolymph of immunized flies at a concentration of 25-50 microM, enough to kill all tested bacteria except Serratia, a Drosophila pathogen [1].
• In Relish mutants, the Cecropin A gene was induced by the G(+) bacteria Micrococcus luteus and Staphylococcus aureus, but not by other G(+) or G(-) bacteria [2].
• PG extracted from M. luteus induced Cecropin A in Relish mutants, whereas PGs from the G(+) bacteria Bacillus megaterium and Bacillus subtilis did not, suggesting that the Drosophila immune system can distinguish PGs from various G(+) bacteria [2].

High impact information on CecA1

• High levels of Rel protein-mediated Cecropin A1 expression previously have been shown to require the GATA site along with the kappaB site [3].
• We provide evidence demonstrating that the GATA motif is needed for expression of the Cecropin A1 gene in larval fat body, but is dispensable in adult fat body [3].
• A nuclear DNA-binding activity interacts with the Cecropin A1 GATA motif with the same properties as the Drosophila GATA factor Serpent [3].
• We now present evidence that the Dif gene product trans-activates the Drosophila Cecropin A1 gene in co-transfection assays [4].
• CecA1 and A2 are most active in larvae and adults; CecB is preferentially active in early pupae [1].

Biological context of CecA1

• Toll10B was found to increase CecA1 transcription, as detected with a cotransfected CecA1-lacZ reporter gene construct [5].
• In this work we report experimental evidence for the direct participation of a GATA motif in the expression of the Drosophila antibacterial peptide gene Cecropin A1 . Previously we have shown that a kappaB-like site is necessary for Cecropin A1 gene expression [6].
• Injection of bacteria induces a 0.8 kb transcript, with expression kinetics similar to that of cecropin [7].
• Of the four putative novel defence proteins (DFPs) annotated by PSI-BLAST three showed similarity to extracellular matrix proteins from vertebrates implicated in innate immunity, while the fourth was similar to, yet distinct from, the anti-microbial protein cecropin [8].

Anatomical context of CecA1

• The genes are strongly expressed in fat body and hemocytes after injection of bacteria, the CecA genes being much more active than CecB in the fat body [1].
• We show that a Drosophila blood cell line contains factors binding specifically to the GATA motif of the Cecropin A1 gene [6].
• Through GmmRel knock-down, we could successfully block the induction of attacin and cecropin expression in the immune responsive tissues fat body and proventriculus (cardia) following microbial challenge [9].

Associations of CecA1 with chemical compounds

• The 34-residue A. aegypti cecropin A is different from the majority of reported insect cecropins in that it is devoid of a tryptophan residue and C-terminal amidation [10].
• Over-expression of the RHD but not full-length RELISH results in an increase in the promoter activity of the cecropin A1 gene in the absence of LPS [11].
• Drosophila cecropin A had strong differential effects on the two maturation forms of Leishmania aethiopica at high concentrations: inhibiting intracellular amastigotes and stimulating extracellular promastigotes to take up thymidine [12].

Physical interactions of CecA1

• In vitro-translated protein from the Rel-only construct specifically binds to the kappa B motif from Drosophila cecropin A1 and Aedes defensin genes [13].

Other interactions of CecA1

• Although the R1 motif was required for Rel protein-mediated CecA1 expression in cotransfection experiments, our data argue against it being a direct target for the Drosophila Rel proteins [14].
• We show that the upstream region of the Cecropin gene CecA1 contains elements responsible for inducible and tissue-specific expression [15].
• The morphogen dorsal (dl) can also activate the Cecropin A1 promoter, but to a lesser extent and in a less sequence-specific manner than Dif [4].
• Both the processing and the nuclear translocation immediately precede the expression of antibacterial peptide genes cecropin A1, attacin, and diptericin [11].

Analytical, diagnostic and therapeutic context of CecA1

• Site-directed mutagenesis of the R1 site diminished Cecropin A1 (CecA1) expression in transgenic Drosophila larvae and flies [14].

References