Abstract
NF-κB transcription factors are crucial for many cellular processes. NF-κB is activated by viral infections to induce expression of antiviral cytokines. Here, we identified a novel member of the human NF-κB family, denoted RelAp43, the nucleotide sequence of which contains several exons as well as an intron of the RelA gene. RelAp43 is expressed in all cell lines and tissues tested and exhibits all the properties of a NF-κB protein. Although its sequence does not include a transactivation domain, identifying it as a class I member of the NF-κB family, it is able to potentiate RelA-mediated transactivation and stabilize dimers comprising p50. Furthermore, RelAp43 stimulates the expression of HIAP1, IRF1, and IFN-β - three genes involved in cell immunity against viral infection. It is also targeted by the matrix protein of lyssaviruses, the agents of rabies, resulting in an inhibition of the NF-κB pathway. Taken together, our data provide the description of a novel functional member of the NF-κB family, which plays a key role in the induction of anti-viral innate immune response.
Highlights
NF-kB proteins comprise a family of structurally-related eukaryotic transcription factors involved in the control of many physiological cellular processes [1]
We demonstrated that RelAp43 induced the expression of genes involved in the innate immune response against viruses
We showed that RelAp43 is targeted by the matrix protein of rabies virus, which contributes to the pathogenesis of the virus and its escape from innate immune response
Summary
NF-kB proteins comprise a family of structurally-related eukaryotic transcription factors involved in the control of many physiological cellular processes [1]. This family contains five major Rel proteins in mammalian cells: p65/RelA, c-Rel, RelB, p50 and p52. All Rel proteins share the N-terminal homology domain (RHD) mediating homo- or hetero-dimerization, DNA binding, nuclear localization and interaction with the IkB proteins, the inhibitors of NF-kB. Activated IKK phosphorylates IkB on specific residues. Free NF-kB dimers enter the nucleus and activate transcription of their target genes by binding specific DNA sequences named kB sites in the promoter region of numerous genes [2]
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