title: Charon Mediates Immune Deficiency-Driven PARP-1-Dependent Immune Responses in Drosophila.
abstract: Regulation of NF-κB nuclear translocation and stability is central to mounting an effective innate immune response. In this article, we describe a novel molecular mechanism controlling NF-κB-dependent innate immune response. We show that a previously unknown protein, termed as Charon, functions as a regulator of antibacterial and antifungal immune defense in Drosophila Charon is an ankyrin repeat-containing protein that mediates poly(ADP-ribose) polymerase-1 (PARP-1)-dependent transcriptional responses downstream of the innate immune pathway. Our results demonstrate that Charon interacts with the NF-κB ortholog Relish inside perinuclear particles and delivers active Relish to PARP-1-bearing promoters, thus triggering NF-κB/PARP-1-dependent transcription of antimicrobial peptides. Ablating the expression of Charon prevents Relish from targeting promoters of antimicrobial genes and effectively suppresses the innate immune transcriptional response. Taken together, these results implicate Charon as an essential mediator of PARP-1-dependent transcription in the innate immune pathway. Thus, to our knowledge, our results are the first to describe the molecular mechanism regulating translocation of the NF-κB subunit from cytoplasm to chromatin.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Yingbiao
authors.identifier: 0000-0001-8266-9178
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Colin
authors.initials: C
authors.lastname: Thomas
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Nikita
authors.initials: N
authors.lastname: Tulin
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Niraj
authors.initials: N
authors.lastname: Lodhi
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Ernest
authors.initials: E
authors.lastname: Boamah
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kolenko
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111 Alexei.Tulin@fccc.edu.
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Tulin
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000276:immunology*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D016328:NF-kappa B; C101626:Rel protein, Drosophila; D014157:Transcription Factors; C000621861:charon protein, Drosophila; D000071137:Poly (ADP-Ribose) Polymerase-1