1887

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Volume 97, Issue 10

Vaccinia virus K1 ankyrin repeat protein inhibits NF-κB activation by preventing RelA acetylation Free

Abstract

The vaccinia virus (VACV) K1 protein inhibits dsRNA-dependent protein kinase (PKR) activation. A consequence of this function is that K1 inhibits PKR-induced NF-κB activation during VACV infection. However, transient expression of K1 also inhibits Toll-like receptor (TLR)-induced NF-κB activation. This suggests that K1 has a second NF-κB inhibitory mechanism that is PKR-independent. This possibility was explored by expressing K1 independently of infection and stimulating NF-κB under conditions that minimized or excluded PKR activation. K1 inhibited both TNF- and phorbol 12-myristate 13-acetate (PMA)-induced NF-κB activation, as detected by transcription of synthetic (e.g. luciferase) and natural (e.g. ) genes controlled by NF-κB. K1 also inhibited NF-κB activity in PKR cells, cells that have greatly decreased amounts of PKR. K1 no longer prevented IκBα degradation or NF-κB nuclear translocation in the absence of PKR, suggesting that K1 acted on a nuclear event. Indeed, K1 was present in the nucleus and cytoplasm of stimulated and unstimulated cells. K1 inhibited acetylation of the RelA (p65) subunit of NF-κB, a nuclear event known to be required for NF-κB activation. Moreover, p65–CBP (CREB-binding protein) interactions were blocked in the presence of K1. However, K1 did not preclude NF-κB binding to oligonucleotides containing κB-binding sites. The current interpretation of these data is that NF-κB–promoter interactions still occur in the presence of K1, but NF-κB cannot properly trigger transcriptional activation because K1 antagonizes acetylation of RelA. Thus, in comparison to all known VACV NF-κB inhibitory proteins, K1 acts at one of the most downstream events of NF-κB activation.

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  • Accepted:
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Keyword(s): ankyrin , K1 , NF-κB , poxvirus , RelA and vaccinia
© Microbiology Society
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2016-10-13
2024-04-20
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Vaccinia virus K1 ankyrin repeat protein inhibits NF-κB activation by preventing RelA acetylation
J. Gen. Virol. 97, 2691 (2016); https://doi.org/10.1099/jgv.0.000576
/content/journal/jgv/10.1099/jgv.0.000576
/content/journal/jgv/10.1099/jgv.0.000576
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