Dataset Information

Signal Integration by the I?B Protein Pickle Shapes Drosophila Innate Host Defense.

ABSTRACT: Pattern recognition receptors are activated following infection and trigger transcriptional programs important for host defense. Tight regulation of NF-?B activation is critical to avoid detrimental and misbalanced responses. We describe Pickle, a Drosophila nuclear I?B that integrates signaling inputs from both the Imd and Toll pathways by skewing the transcriptional output of the NF-?B dimer repertoire. Pickle interacts with the NF-?B protein Relish and the histone deacetylase dHDAC1, selectively repressing Relish homodimers while leaving other NF-?B dimer combinations unscathed. Pickle's ability to selectively inhibit Relish homodimer activity contributes to proper host immunity and organismal health. Although loss of pickle results in hyper-induction of Relish target genes and improved host resistance to pathogenic bacteria in the short term, chronic inactivation of pickle causes loss of immune tolerance and shortened lifespan. Pickle therefore allows balanced immune responses that protect from pathogenic microbes while permitting the establishment of beneficial commensal host-microbe relationships.

SUBMITTER: Morris O

PROVIDER: S-EPMC5026699 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Publications

Signal Integration by the IκB Protein Pickle Shapes Drosophila Innate Host Defense.

Morris Otto O Liu Xi X Domingues Celia C Runchel Christopher C Chai Andrea A Basith Shaherin S Tenev Tencho T Chen Haiyang H Choi Sangdun S Pennetta Giuseppa G Buchon Nicolas N Meier Pascal P

Cell host & microbe 20160901 3

Pattern recognition receptors are activated following infection and trigger transcriptional programs important for host defense. Tight regulation of NF-κB activation is critical to avoid detrimental and misbalanced responses. We describe Pickle, a Drosophila nuclear IκB that integrates signaling inputs from both the Imd and Toll pathways by skewing the transcriptional output of the NF-κB dimer repertoire. Pickle interacts with the NF-κB protein Relish and the histone deacetylase dHDAC1, selectiv ...[more]

PMID: 27631699

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Project description:It has been acknowledged that source databases recording experimentally supported human protein-protein interactions (PPIs) exhibit limited overlap. Thus, the reconstruction of a comprehensive PPI network requires appropriate integration of multiple heterogeneous primary datasets, presenting the PPIs at various genetic reference levels. Existing PPI meta-databases perform integration via normalization; namely, PPIs are merged after converted to a certain target level. Hence, the node set of the integrated network depends each time on the number and type of the combined datasets. Moreover, the irreversible a priori normalization process hinders the identification of normalization artifacts in the integrated network, which originate from the nonlinearity characterizing the genetic information flow. PICKLE (Protein InteraCtion KnowLedgebasE) 2.0 implements a new architecture for this recently introduced human PPI meta-database. Its main novel feature over the existing meta-databases is its approach to primary PPI dataset integration via genetic information ontology. Building upon the PICKLE principles of using the reviewed human complete proteome (RHCP) of UniProtKB/Swiss-Prot as the reference protein interactor set, and filtering out protein interactions with low probability of being direct based on the available evidence, PICKLE 2.0 first assembles the RHCP genetic information ontology network by connecting the corresponding genes, nucleotide sequences (mRNAs) and proteins (UniProt entries) and then integrates PPI datasets by superimposing them on the ontology network without any a priori transformations. Importantly, this process allows the resulting heterogeneous integrated network to be reversibly normalized to any level of genetic reference without loss of the original information, the latter being used for identification of normalization biases, and enables the appraisal of potential false positive interactions through PPI source database cross-checking. The PICKLE web-based interface (www.pickle.gr) allows for the simultaneous query of multiple entities and provides integrated human PPI networks at either the protein (UniProt) or the gene level, at three PPI filtering modes.

Dataset Information

Signal Integration by the I?B Protein Pickle Shapes Drosophila Innate Host Defense.

Publications

Signal Integration by the IκB Protein Pickle Shapes Drosophila Innate Host Defense.

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