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NF-κB and AP-1 Connection: Mechanism of NF-κB-Dependent Regulation of AP-1 Activity

  • Fujioka, Shuichi Department of Molecular and Cellular Oncology
  • Niu, Jiangong The Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas
  • Schmidt, Christian Department of Molecular and Cellular Oncology
  • Sclabas, Guido M. Department of Visceral and Transplantation Surgery, Inselspital, University of Bern, Bern, Switzerland
  • Peng, Bailu Department of Molecular and Cellular Oncology
  • Uwagawa, Tadashi Department of Surgical Oncology
  • Li, Zhongkui Department of Surgical Oncology
  • Evans, Douglas B. Department of Surgical Oncology
  • Abbruzzese, James L. Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center
  • Chiao, Paul J. The Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas
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Published in:
  • Molecular and Cellular Biology. - American Society for Microbiology. - 2004, vol. 24, no. 17, p. 7806-7819
Cell Biology
Molecular Biology
English ABSTRACT
Nuclear factor κB (NF-κB) and activator protein 1 (AP-1) transcription factors regulate many important biological and pathological processes. Activation of NF-κB is regulated by the inducible phosphorylation of NF-κB inhibitor IκB by IκB 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-κB and AP-1 may modulate each other, thus expanding the scope of these two rapidly inducible transcription factors. To determine whether NF-κB 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/IκBαM 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-κB downstream target genes. Inhibition of NF-κB 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-κB in participating in the regulation of elk-1, c-fos, and VEGF expression.
Language
  • English
Open access status
bronze
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https://sonar.ch/global/documents/418
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