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NF-kappaB and AP-1 connection: mechanism of NF-kappaB-dependent regulation of AP-1 activity.

Publication ,  Journal Article
Fujioka, S; Niu, J; Schmidt, C; Sclabas, GM; Peng, B; Uwagawa, T; Li, Z; Evans, DB; Abbruzzese, JL; Chiao, PJ
Published in: Mol Cell Biol
September 2004

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.

Duke Scholars

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

September 2004

Volume

24

Issue

17

Start / End Page

7806 / 7819

Location

United States

Related Subject Headings

  • ets-Domain Protein Elk-1
  • Vascular Endothelial Growth Factor A
  • Transcription Factors
  • Transcription Factor AP-1
  • Stem Cells
  • Signal Transduction
  • Reactive Oxygen Species
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins
 

Citation

APA
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ICMJE
MLA
NLM
Fujioka, S., Niu, J., Schmidt, C., Sclabas, G. M., Peng, B., Uwagawa, T., … Chiao, P. J. (2004). NF-kappaB and AP-1 connection: mechanism of NF-kappaB-dependent regulation of AP-1 activity. Mol Cell Biol, 24(17), 7806–7819. https://doi.org/10.1128/MCB.24.17.7806-7819.2004
Fujioka, Shuichi, Jiangong Niu, Christian Schmidt, Guido M. Sclabas, Bailu Peng, Tadashi Uwagawa, Zhongkui Li, Douglas B. Evans, James L. Abbruzzese, and Paul J. Chiao. “NF-kappaB and AP-1 connection: mechanism of NF-kappaB-dependent regulation of AP-1 activity.Mol Cell Biol 24, no. 17 (September 2004): 7806–19. https://doi.org/10.1128/MCB.24.17.7806-7819.2004.
Fujioka S, Niu J, Schmidt C, Sclabas GM, Peng B, Uwagawa T, et al. NF-kappaB and AP-1 connection: mechanism of NF-kappaB-dependent regulation of AP-1 activity. Mol Cell Biol. 2004 Sep;24(17):7806–19.
Fujioka, Shuichi, et al. “NF-kappaB and AP-1 connection: mechanism of NF-kappaB-dependent regulation of AP-1 activity.Mol Cell Biol, vol. 24, no. 17, Sept. 2004, pp. 7806–19. Pubmed, doi:10.1128/MCB.24.17.7806-7819.2004.
Fujioka S, Niu J, Schmidt C, Sclabas GM, Peng B, Uwagawa T, Li Z, Evans DB, Abbruzzese JL, Chiao PJ. NF-kappaB and AP-1 connection: mechanism of NF-kappaB-dependent regulation of AP-1 activity. Mol Cell Biol. 2004 Sep;24(17):7806–7819.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

September 2004

Volume

24

Issue

17

Start / End Page

7806 / 7819

Location

United States

Related Subject Headings

  • ets-Domain Protein Elk-1
  • Vascular Endothelial Growth Factor A
  • Transcription Factors
  • Transcription Factor AP-1
  • Stem Cells
  • Signal Transduction
  • Reactive Oxygen Species
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins