Abstract
Nuclear factor κB (NF-κB) plays an essential role in regulation of innate immunity. In mammals, NF-κB factors can form homodimers and heterodimers to activate gene expression. In insects, three NF-κB factors, Dorsal, Dif and Relish, have been identified to activate antimicrobial peptide (AMP) gene expression. However, it is not clear whether Dorsal (or Dif) and Relish can form heterodimers. Here we report the identification and functional analysis of a Dorsal homologue (MsDorsal) and two Relish short isoforms (MsRel2A and MsRel2B) from the tobacco hornworm, Manduca sexta. Both MsRel2A and MsRel2B contain only a Rel homology domain (RHD) and lack the ankyrin-repeat inhibitory domain. Overexpression of the RHD domains of MsDorsal and MsRel2 in Drosophila melanogaster S2 and Spodoptera frugiperda Sf9 cells can activate AMP gene promoters from M. sexta and D. melanogaster. We for the first time confirmed the interaction between MsDorsal-RHD and MsRel2-RHD, and suggesting that Dorsal and Rel2 may form heterodimers. More importantly, co-expression of MsDorsal-RHD with MsRel2-RHD suppressed activation of several M. sexta AMP gene promoters. Our results suggest that the short MsRel2 isoforms may form heterodimers with MsDorsal as a novel mechanism to prevent over-activation of antimicrobial peptides.
Highlights
NF-κ B factors have been identified in the phylum of arthropoda[19,20,21,22,23,24,25,26,27,28,29,30,31]
We showed for the first time that co-expression of MsDorsal and MsRel[2] suppressed the expression of antimicrobial peptide (AMP) gene promoters
Our results suggest that active Relish short isoforms such as MsRel2A and MsRel2B can activate AMP genes as homodimers, and they may form heterodimers with MsDorsal as a novel mechanism to negatively regulate AMP gene expression to prevent over-activation of AMPs
Summary
NF-κ B factors have been identified in the phylum of arthropoda[19,20,21,22,23,24,25,26,27,28,29,30,31]. Mori, two Rel (Dorsal) proteins, BmRelA and BmRelB, activate antimicrobial peptide genes differently[24], and two Relish homologs (BmRelish[1] and 2) have been identified[23], and BmRelish[2] isoform is a dominant negative regulator of the active BmRelish[123]. The two short isoforms of M. sexta Relish, named MsRel2A and MsRel2B, contain only an RHD domain and lack the ankyrin-repeat inhibitory domain. Both MsRel2A and MsRel2B can activate AMP gene promoters. Our results suggest that active Relish short isoforms such as MsRel2A and MsRel2B can activate AMP genes as homodimers, and they may form heterodimers with MsDorsal as a novel mechanism to negatively regulate AMP gene expression to prevent over-activation of AMPs
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