Tumor necrosis factor alpha induces the expression of the nuclear protein p8 via a novel NF kappaB binding site within the promoter.
p8 is a widely expressed HMG-I/Y-like transcription factor which is involved in regulating cell proliferation and tissue stress. Several studies describe a strong upregulation of p8 expression during inflammatory processes like pancreatitis and LPS-induced sepsis. Here we demonstrate that TNFalpha, which is an important inducer of innate defence against gram-negative bacteria, significantly stimulates p8 protein production in H4IIE rat hepatoma cells within 2 hours. Since a putative NF kappaB motif has been described, we further tested whether TNFalpha stimulates p8 expression via activation of NF kappaB. We characterized the TNFalpha-induced binding of NF kappaB to this motif. We show that the TNFalpha-induced NF kappaB pathway contributes to the induction of p8 during pancreatitis and LPS-induced inflammation.
Kallwellis
K
K
Institut für Medizinische Biochemie und Molekularbiologie, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany.
Grempler
R
R
Günther
S
S
Päth
G
G
Walther
R
R
D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017384:Sequence Deletion; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; C491644:Nupr1 protein, mouse; D014409:Tumor Necrosis Factor-alpha