The tumor suppressor gene WWOX links the canonical and noncanonical NF-κB pathways in HTLV-I Tax-mediated tumorigenesis.

نویسندگان

  • Jing Fu
  • Zhaoxia Qu
  • Pengrong Yan
  • Chie Ishikawa
  • Rami I Aqeilan
  • Arnold B Rabson
  • Gutian Xiao
چکیده

Both the canonical and noncanonical nuclear factor κB (NF-κB) 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-κB pathway significantly delays tumorigenesis mediated by the viral oncoprotein Tax. One function of noncanonical NF-κB 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-κB pathway. Mechanistic studies indicated that WWOX blocked Tax-induced inhibitors of κB kinaseα (IKKα) recruitment to RelA and subsequent RelA phosphorylation at S536. In contrast, WWOX Y33R, a mutant unable to block the IKKα 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-κB pathways for tumorigenesis. These data also suggest a novel role of WWOX in NF-κB regulation and viral tumorigenesis.

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The tumor suppressor gene wwox links the canonical and non-canonical NF-κB pathways in HTLV-I Tax-mediated tumorigenesis Running title: WWOX in Tax tumorigenesis

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LYMPHOID NEOPLASIA The tumor suppressor gene WWOX links the canonical and noncanonical NF- B pathways in HTLV-I Tax-mediated tumorigenesis

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عنوان ژورنال:
  • Blood

دوره 117 5  شماره 

صفحات  -

تاریخ انتشار 2011