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C/EBP{delta} and STAT-1 are required for TLR8 transcriptional activity.

ABSTRACT: Toll-like receptor 8 (TLR8), which is expressed primarily in myeloid cells, plays a central role in initiating immune responses to viral single-stranded RNA. Despite the great interest in the field of TLR8 research, very little is known in terms of TLR8 biology and its transcriptional regulation. Here, we describe the isolation of the hTLR8 promoter and the characterization of the molecular mechanisms involved in its regulation. Reporter gene analysis and ChIP assays demonstrated that the hTLR8 regulation of the basal transcription is regulated via three C/EBP cis-acting elements that required C/EBPδ and C/EBPβ activity. In addition, we observed that R848 stimulation increases TLR8 transcriptional activity via an enhanced binding of C/EBPδ, and not C/EBPβ, to its responsive sites within the TLR8 promoter. Moreover, we showed that IFN-γ also increased TLR8 transcription activity via the binding of STAT1 transcription factor to IFN-γ activated sequence elements on the TLR8 promoter and enhanced TLR8 functionality. These results shed new light on the mechanisms involved during TLR8-mediated innate immune response.

SUBMITTER: Zannetti C

PROVIDER: S-EPMC2966093 | biostudies-literature |

REPOSITORIES: biostudies-literature

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PARP-1 Controls the Adipogenic Transcriptional Program by PARylating C/EBP? and Modulating Its Transcriptional Activity.

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| S-EPMC5258183 | biostudies-literature

Hipk is required for JAK/STAT activity during development and tumorigenesis.

Project description:Drosophila has been instrumental as a model system in studying signal transduction and revealing molecular functions in development and human diseases. A point mutation in the Drosophila Janus kinase JAK (called hop) causes constitutive activation of the JAK/STAT pathway. We provide robust genetic evidence that the Homeodomain interacting protein kinase (Hipk) is required for endogenous JAK/STAT activity. Overexpression of Hipk can phenocopy the effects of overactive JAK/STAT mutations and lead to melanized tumors, and loss of Hipk can suppress the effects of hyperactive JAK/STAT. Further, the loss of the pathway effector Stat92E can suppress Hipk induced overgrowth. Interaction studies show that Hipk can physically interact with Stat92E and regulate Stat92E subcellular localization. Together our results show that Hipk is a novel factor required for effective JAK/STAT signaling.

| S-EPMC6938406 | biostudies-literature

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| S-EPMC6105679 | biostudies-literature

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| S-EPMC307392 | biostudies-other

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THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors.

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| S-EPMC5290269 | biostudies-literature

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| S-EPMC6080926 | biostudies-literature

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