NF-kappaB and AP-1 connection: mechanism of NF-kappaB-dependent regulation of AP-1 activity.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Fujioka, S; Niu, J; Schmidt, C; Sclabas, GM; Peng, B; Uwagawa, T; Li, Z; Evans, DB; Abbruzzese, JL; Chiao, PJ
Published Date
- September 2004
Published In
Volume / Issue
- 24 / 17
Start / End Page
- 7806 - 7819
PubMed ID
- 15314185
Pubmed Central ID
- PMC507000
International Standard Serial Number (ISSN)
- 0270-7306
Digital Object Identifier (DOI)
- 10.1128/MCB.24.17.7806-7819.2004
Language
- eng
Conference Location
- United States