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. 2018 Feb 2;68(2):347–358. doi: 10.1136/gutjnl-2017-315348

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TonEBP and YY1 interact via RHD and spacer. (A) Diagrams of TonEBP and YY1 and their deletion constructs. (B–E) Lysates from HEK293 cells transfected with Myc-TonEBP plus Flag-YY1 (B) or various recombinant fragment of Flag-YY1 (C), Myc-Yc1 plus or Flag-YY1 or Flag-YY1-ΔS (D) or Flag-YY1 plus Myc-TonEBP or Myc-TonEBP-ΔRHD (E) were immunoprecipitated with normal IgG, anti-Flag IgG or anti-Myc IgG as indicated. The immunoprecipitates (upper) and lysates (bottom) were immunoblotted as indicated. (F) Model of TonEBP actions in the pathogenesis of HCC. First, TonEBP mediates oxidative stress-induced cell injury and local inflammation. Second, TonEBP expression is enhanced by oxidative stress. On the promoter of the COX-2 gene, the elevated TonEBP recruits the acetyltransferase p300 to YY1 in a manner dependent on IL-1β. TonEBP promotes tumourigenesis, recurrence and metastasis via PGE₂ and possibly other pathways (broken line). See text for details. COX-2, cyclo-oxygenase-2; Flag, anti-Flag IgG; GA rich, glycine-alanin rich; GK rich, glycine-lysine rich; HCC, hepatocellular carcinoma; IB, immunoblot; IgG, normal IgG, Myc, anti-Myc IgG; PGE₂, prostaglandin E₂; IL, interleukin; IP, immunoprecipitated; LPS, lipopolysaccharide; RHD, Rel-homology domain; TonEBP, tonicity-responsive enhancer-binding protein.