Involvement of GSK-3beta in TWEAK-mediated NF-kappaB activation.
Glycogen synthase kinase-3beta (GSK-3beta) is a key component of several signaling pathways. We found that a short variant of 'TNF-like weak inducer of apoptosis' (shortTWEAK) formed a complex with GSK-3beta in a yeast two-hybrid system. We demonstrate that shortTWEAK and GSK-3beta colocalize in the nucleus of human neuroblastoma cells. We also show that TWEAK is internalized in different cell lines and that it translocates to the nucleus. This event causes the degradation of IkappaBalpha, the nuclear translocation of both GSK-3beta and p65, and the induction of NF-kappaB-driven gene expression. We demonstrate that the induction of IL-8 expression by TWEAK can be counteracted by LiCl. Taken together, these data suggest that GSK-3beta plays an important role in the signal transduction pathway between TWEAK and NF-kappaB.
De Ketelaere
Adelheid
A
Enabling Technologies, Johnson & Johnson Pharmaceutical Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Vermeulen
Linda
L
Vialard
Jorge
J
Van De Weyer
Inez
I
Van Wauwe
Jean
J
Haegeman
Guy
G
Moelans
Inge
I
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D000074049:Cytokine TWEAK; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D018021:Lithium Chloride / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D021381:Protein Transport; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048069:Tumor Necrosis Factors; D020798:Two-Hybrid System Techniques
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D000074049:Cytokine TWEAK; D004791:Enzyme Inhibitors; D016209:Interleukin-8; D016328:NF-kappa B; D011994:Recombinant Proteins; C109743:TNFSF12 protein, human; C491645:Tnfsf12 protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride