| First Author | Fu J | Year | 2011 |
| Journal | Blood | Volume | 117 |
| Issue | 5 | Pages | 1652-61 |
| PubMed ID | 21115974 | Mgi Jnum | J:170371 |
| Mgi Id | MGI:4946370 | Doi | 10.1182/blood-2010-08-303073 |
| Citation | Fu J, et al. (2011) The tumor suppressor gene WWOX links the canonical and noncanonical NF-kappaB pathways in HTLV-I Tax-mediated tumorigenesis. Blood 117(5):1652-61 |
| abstractText | Both the canonical and noncanonical nuclear factor kappaB (NF-kappaB) pathways have been linked to tumorigenesis. However, it remains unknown whether and how the 2 signaling pathways cooperate during tumorigenesis. We report that inhibition of the noncanonical NF-kappaB pathway significantly delays tumorigenesis mediated by the viral oncoprotein Tax. One function of noncanonical NF-kappaB activation was to repress expression of the WWOX tumor suppressor gene. Notably, WWOX specifically inhibited Tax-induced activation of the canonical, but not the noncanonical NF-kappaB pathway. Mechanistic studies indicated that WWOX blocked Tax-induced inhibitors of kappaB kinasealpha (IKKalpha) recruitment to RelA and subsequent RelA phosphorylation at S536. In contrast, WWOX Y33R, a mutant unable to block the IKKalpha recruitment and RelA phosphorylation, lost the ability to inhibit Tax-mediated tumorigenesis. These data provide one important mechanism by which Tax coordinates the 2 NF-kappaB pathways for tumorigenesis. These data also suggest a novel role of WWOX in NF-kappaB regulation and viral tumorigenesis. |
