Functional cooperation between JunD and NF-kappaB in rat hepatocytes.
AP-1 and NF-kappaB are rapidly activated during liver regeneration. Whether these parallel inductions have potential functional implications is not known. Isolated rat hepatocytes were stimulated with two mitogens, epidermal growth factor or hepatocyte growth factor and with tumor necrosis factor alpha, a cytokine involved in the liver regenerative response in vivo and a strong inducer of NF-kappaB. All three cytokines increased AP-1 and NF-kappaB binding to their cognate cis-element and induced a 2.5-fold activation of NF-kappaB-dependent transcription. Inactivation of AP-1 by TAM67, a dominant negative mutant of AP-1 drastically inhibited basal and cytokine-induced NF-kappaB transactivation. Overexpression of Jun D, but not of the other Jun or Fos proteins increased by threefold NF-kappaB transactivation. Functional cooperation between JunD and p65 was demonstrated in a simple Gal-hybrid system. Finally, a twofold decrease in NF-kappaB transactivation was found in hepatocytes isolated from JunD(-/-) mice compared with hepatocytes from JunD(+/+) mice. Altogether these data demonstrate a functional cooperation of p65 with JunD, a major constituent of AP-1 in normal hepatocytes.
Rahmani
M
M
Laboratoire de Biologie cellulaire, INSERM U 327, Faculté de Médecine Xavier Bichat et Université Paris 7 Denis Diderot, Paris, France.
Péron
P
P
Weitzman
J
J
Bakiri
L
L
Lardeux
B
B
Bernuau
D
D
D000818:Animals; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005799:Genes, Dominant; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism*; D008099:Liver / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000494:pharmacology; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D017228:Hepatocyte Growth Factor