title: TNF-alpha mediated NF-kappaB activation is constantly extended by transglutaminase 2.
abstract: Increased levels of transglutaminase 2 (TGase 2) expression have been reported in many inflammatory diseases, as well as in drug resistant cancer cells. Previous reports have shown that TGase 2 is capable of inducing nuclear factor-kappaB (NF-kappaB) activation via depletion of inhibitor of kappaB (I-kappaB)alpha through polymerization in the absence of I-kappaBalpha kinase activation. This raises the question of whether increased expression of TGase 2 can extend NF-kappaB activation mediated by a canonical activation pathway. In the TGase 2-inducible EcR23/TG cell line, TGase 2 over-expression resulted in sustained activation of NF-kappa B in the presence of TNF-alpha, for up to 24 hrs, while in the absence of TGase 2 induction, NF-kappaB activity was restored to basal levels within 6 hrs of TNF-alpha treatment. In mice injected with an adenovirus vector expressing TGase 2, NF-kappaB was constitutively activated for up to 5 days, whereas Adeno/GFP-injected mice exhibited attenuated activation of NF-kappaB in response to TNF-alpha stress. Thus, the presence of increased levels of TGase 2 may exacerbate NF-kappa B activation in inflammatory states.
authors.affiliation: Cancer Cell and Molecular Biology Branch, Goyang, Gyeonggi-do, Republic of Korea.
authors.forename: Kang-Seo
authors.initials: KS
authors.lastname: Park
authors.forename: Dae-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Chunkyu
authors.initials: C
authors.lastname: Ko
authors.forename: Sang-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Oh
authors.forename: Soo-Youl
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000256:Adenoviridae; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003538:Cystamine / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D003538:Cystamine