Mol Cell Biol 2004,
Fujioka, Shuichi; Niu, Jiangong; Schmidt, Christian; Sclabas, Guido M; Peng, Bailu; Uwagawa, Tadashi; Li, Zhongkui; Evans, Douglas B; Abbruzzese, James L; Chiao, Paul J
Nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1) transcription factors regulate many important biological and pathological processes. Activation of NF-kappaB is regulated by the inducible phosphorylation of NF-kappaB inhibitor IkappaB by IkappaB kinase. In contrast, Fos, a key component of AP-1, is primarily transcriptionally regulated by serum responsive factors (SRFs) and ternary complex factors (TCFs). Despite these different regulatory mechanisms, there is an intriguing possibility that NF-kappaB and AP-1 may modulate each other, thus expanding the scope of these two rapidly inducible transcription factors. To determine whether NF-kappaB activity is involved in the regulation of fos expression in response to various stimuli, we analyzed activity of AP-1 and expression of fos, fosB, fra-1, fra-2, jun, junB, and junD, as well as AP-1 downstream target gene VEGF, using MDAPanc-28 and MDAPanc-28/IkappaBalphaM pancreatic tumor cells and wild-type, IKK1-/-, and IKK2-/- murine embryonic fibroblast cells. Our results show that elk-1, a member of TCFs, is one of the NF-kappaB downstream target genes. Inhibition of NF-kappaB activity greatly decreased expression of elk-1. Consequently, the reduced level of activated Elk-1 protein by extracellular signal-regulated kinase impeded constitutive, serum-, and superoxide-inducible c-fos expression. Thus, our study revealed a distinct and essential role of NF-kappaB in participating in the regulation of elk-1, c-fos, and VEGF expression.
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Text Mining Data
AP-1 → NF-kappaB: " NF-kappaB and AP-1 connection : mechanism of NF-kappaB
dependent regulation of AP-1
VEGF ⊣ NF-kappaB: " Thus, our study revealed a distinct and essential role of NF-kappaB in participating in the regulation of elk-1, c-fos, and VEGF expression "
elk-1 → NF-kappaB: " Thus, our study revealed a distinct and essential role of NF-kappaB in participating in the regulation of elk-1 , c-fos, and VEGF expression "
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