dRYBP contributes to the negative regulation of the Drosophila Imd pathway.
The Drosophila humoral innate immune response fights infection by producing antimicrobial peptides (AMPs) through the microbe-specific activation of the Toll or the Imd signaling pathway. Upon systemic infection, the production of AMPs is both positively and negatively regulated to reach a balanced...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3626645?pdf=render |
| _version_ | 1818422853987467264 |
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| author | Ricardo Aparicio Claudine Neyen Bruno Lemaitre Ana Busturia |
| author_facet | Ricardo Aparicio Claudine Neyen Bruno Lemaitre Ana Busturia |
| author_sort | Ricardo Aparicio |
| collection | DOAJ |
| description | The Drosophila humoral innate immune response fights infection by producing antimicrobial peptides (AMPs) through the microbe-specific activation of the Toll or the Imd signaling pathway. Upon systemic infection, the production of AMPs is both positively and negatively regulated to reach a balanced immune response required for survival. Here, we report the function of the dRYBP (drosophila Ring and YY1 Binding Protein) protein, which contains a ubiquitin-binding domain, in the Imd pathway. We have found that dRYBP contributes to the negative regulation of AMP production: upon systemic infection with Gram-negative bacteria, Diptericin expression is up-regulated in the absence of dRYBP and down-regulated in the presence of high levels of dRYBP. Epistatic analyses using gain and loss of function alleles of imd, Relish, or skpA and dRYBP suggest that dRYBP functions upstream or together with SKPA, a member of the SCF-E3-ubiquitin ligase complex, to repress the Imd signaling cascade. We propose that the role of dRYBP in the regulation of the Imd signaling pathway is to function as a ubiquitin adaptor protein together with SKPA to promote SCF-dependent proteasomal degradation of Relish. Beyond the identification of dRYBP as a novel component of Imd pathway regulation, our results also suggest that the evolutionarily conserved RYBP protein may be involved in the human innate immune response. |
| first_indexed | 2024-12-14T13:32:52Z |
| format | Article |
| id | doaj.art-0108e893913b46258428c0328c06d5c8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T13:32:52Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0108e893913b46258428c0328c06d5c82022-12-21T22:59:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6205210.1371/journal.pone.0062052dRYBP contributes to the negative regulation of the Drosophila Imd pathway.Ricardo AparicioClaudine NeyenBruno LemaitreAna BusturiaThe Drosophila humoral innate immune response fights infection by producing antimicrobial peptides (AMPs) through the microbe-specific activation of the Toll or the Imd signaling pathway. Upon systemic infection, the production of AMPs is both positively and negatively regulated to reach a balanced immune response required for survival. Here, we report the function of the dRYBP (drosophila Ring and YY1 Binding Protein) protein, which contains a ubiquitin-binding domain, in the Imd pathway. We have found that dRYBP contributes to the negative regulation of AMP production: upon systemic infection with Gram-negative bacteria, Diptericin expression is up-regulated in the absence of dRYBP and down-regulated in the presence of high levels of dRYBP. Epistatic analyses using gain and loss of function alleles of imd, Relish, or skpA and dRYBP suggest that dRYBP functions upstream or together with SKPA, a member of the SCF-E3-ubiquitin ligase complex, to repress the Imd signaling cascade. We propose that the role of dRYBP in the regulation of the Imd signaling pathway is to function as a ubiquitin adaptor protein together with SKPA to promote SCF-dependent proteasomal degradation of Relish. Beyond the identification of dRYBP as a novel component of Imd pathway regulation, our results also suggest that the evolutionarily conserved RYBP protein may be involved in the human innate immune response.http://europepmc.org/articles/PMC3626645?pdf=render |
| spellingShingle | Ricardo Aparicio Claudine Neyen Bruno Lemaitre Ana Busturia dRYBP contributes to the negative regulation of the Drosophila Imd pathway. PLoS ONE |
| title | dRYBP contributes to the negative regulation of the Drosophila Imd pathway. |
| title_full | dRYBP contributes to the negative regulation of the Drosophila Imd pathway. |
| title_fullStr | dRYBP contributes to the negative regulation of the Drosophila Imd pathway. |
| title_full_unstemmed | dRYBP contributes to the negative regulation of the Drosophila Imd pathway. |
| title_short | dRYBP contributes to the negative regulation of the Drosophila Imd pathway. |
| title_sort | drybp contributes to the negative regulation of the drosophila imd pathway |
| url | http://europepmc.org/articles/PMC3626645?pdf=render |
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