| First Author | Randall CM | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 5 | Pages | 2371-9 |
| PubMed ID | 22301546 | Mgi Jnum | J:181352 |
| Mgi Id | MGI:5311076 | Doi | 10.4049/jimmunol.1100136 |
| Citation | Randall CM, et al. (2012) The MC159 Protein from the Molluscum Contagiosum Poxvirus Inhibits NF-kappaB Activation by Interacting with the IkappaB Kinase Complex. J Immunol 188(5):2371-9 |
| abstractText | Molluscum contagiosum virus (MCV) causes persistent neoplasms in healthy and immunocompromised people. Its ability to persist likely is due to its arsenal of viral immunoevasion proteins. For example, the MCV MC159 protein inhibits TNF-R1-induced NF-kappaB activation and apoptosis. The MC159 protein is a viral FLIP and, as such, possesses two tandem death effector domains (DEDs). We show in this article that, in human embryonic kidney 293 T cells, the expression of wild-type MC159 or a mutant MC159 protein containing the first DED (MC159 A) inhibited TNF-induced NF-kappaB, or NF-kappaB activated by PMA or MyD88 overexpression, whereas a mutant protein lacking the first DED (MC159 B) did not. We hypothesized that the MC159 protein targeted the IkappaB kinase (IKK) complex to inhibit these diverse signaling events. Indeed, the MC159 protein, but not MC159 B, coimmunoprecipitated with IKKgamma. MC159 coimmunoprecipitated with IKKgamma when using mouse embryonic fibroblasts that lack either IKKalpha or IKKbeta, suggesting that the MC159 protein interacted directly with IKKgamma. MC159-IKKgamma coimmunoprecipitations were detected during infection of cells with either MCV isolated from human lesions or with a recombinant MC159-expressing vaccinia virus. MC159 also interacts with TRAF2, a signaling molecule involved in NF-kappaB activation. However, mutational analysis of MC159 failed to reveal a correlation between MC159-TRAF2 interactions and MC159's inhibitory function. We propose that MC159-IKK interactions, but not MC159-TRAF2 interactions, are responsible for inhibiting NF-kappaB activation. |
