Interruption of NFκB-Stat1 signaling mediates EGF-induced cell-cycle arrest

Masafumi Ohtsubo, Atsushi Takayanaci, Shinobu Gamou, Nobuyoshi Shimizu

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

It is known that EGF induces the cell-cycle arrest in A431 cells that possess high numbers of EGF receptors and it was previously suggested that p21/WAF1 protein was a major effector molecule of the EGF-mediated cell-cycle arrest of A431 cells. Here, we further investigate this phenomenon using the decoy double-strand oligonucleotides for STAT-binding sequence (STAT decoy) and IκB, an inhibitor of the nuclear factor kappa B (NFκB). Addition of STAT decoy restored EGF-induced A431 cell-growth arrest. Interestingly, infection of adenovirus vectors to express IκB (AxlκBαΔN) as the inhibitor of NFκB also reversed the A431 cell-growth inhibition. The individual treatment of two inhibitors partially inhibited the WAF1 gene expression, whereas simultaneous treatment of two inhibitors exhibited more efficient inhibition. These observations suggest the activation of NFκB via IκB degradation and STAT1 via specific receptor kinase activity synergistically induce WAF1 gene expression in A431 cells. Thus, NFκB and STAT1 pathways mutually interact to play an important role in the EGF-induced intracellular reaction. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)131-137
Number of pages7
JournalJournal of Cellular Physiology
Volume184
Issue number1
Publication statusPublished - 2000

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NF-kappa B
Cell Cycle Checkpoints
Epidermal Growth Factor
Cells
Cell growth
Gene expression
Adenoviridae Infections
Gene Expression
Oligonucleotides
Growth
Phosphotransferases
Chemical activation
Degradation
Molecules
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Ohtsubo, M., Takayanaci, A., Gamou, S., & Shimizu, N. (2000). Interruption of NFκB-Stat1 signaling mediates EGF-induced cell-cycle arrest. Journal of Cellular Physiology, 184(1), 131-137.

Interruption of NFκB-Stat1 signaling mediates EGF-induced cell-cycle arrest. / Ohtsubo, Masafumi; Takayanaci, Atsushi; Gamou, Shinobu; Shimizu, Nobuyoshi.

In: Journal of Cellular Physiology, Vol. 184, No. 1, 2000, p. 131-137.

Research output: Contribution to journalArticle

Ohtsubo, M, Takayanaci, A, Gamou, S & Shimizu, N 2000, 'Interruption of NFκB-Stat1 signaling mediates EGF-induced cell-cycle arrest', Journal of Cellular Physiology, vol. 184, no. 1, pp. 131-137.
Ohtsubo, Masafumi ; Takayanaci, Atsushi ; Gamou, Shinobu ; Shimizu, Nobuyoshi. / Interruption of NFκB-Stat1 signaling mediates EGF-induced cell-cycle arrest. In: Journal of Cellular Physiology. 2000 ; Vol. 184, No. 1. pp. 131-137.
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