Abstract NF-kB is a transcription factor that regulates the expression

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Abstract
NF-B is a transcription factor that regulates the expression of several immunoregulatory
genes, including genes that control pro-inflammatory cytokines. Poxviruses, and many
other viruses, evade these responses by encoding proteins that inhibit NF-B activation.
One such protein is the vaccinia virus K1 protein, which consists of ankyrin (ANK)
repeats. Recently, our lab demonstrated that the K1 protein inhibits NF-B activation by
inhibiting PKR, an upstream activator of NF-B. However, we believe that the K1
protein possesses a second NF-B inhibitory mechanism. First, we found that the K1
crystal structure is significantly similar to an inhibitor of NF-B, IBα. Moreover,
ectopically expressed K1 protein inhibits TNF and PMA induced NF-B activation,
which function independently of PKR activation. K1 was found to localize to both the
nucleus and cytoplasm. In addition, the K1 protein was found to co-immunoprecipitate
with NF-B. Based on this preliminary data we hypothesize that the K1 protein binds to
the inactivated NF-B complex via its ANK repeats to inhibit its activation by affecting
DNA binding or post-translational modifications. To test our hypothesis we will evaluate
several K1 mutant proteins for their ability to bind to and inhibit NF-B. We hypothesize
that the mutants that lose the ability to bind to NF-B will no longer inhibit its activation.
This will elucidate another mechanism by which the K1 protein inhibits this pathway.
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