H2O2-induced AP-1 activation and its effect on p21WAF1/CIP1-mediated G2/M arrest in a p53-deficient human lung cancer cell

Youn Wook Chung, Dae won Jeong, Joo Yun Won, Eui Ju Choi, Yung Hyun Choi, Ick Young Kim

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Cellular response to oxidative stress is a complex process that is often connected to cell cycle regulation. The present study examines the effect of H2O2 on cell cycle regulation and involvement of reactive oxygen species (ROS) in these H2O2-induced responses in a p53-deficient human lung carcinoma cell line, H1299. Treatment of the cells with H2O2 caused a G2/M phase arrest. Among the redox-sensitive transcription factors, NF-κB and AP-1, we found that only AP-1 was activated by 200μM H2O2 in human lung cells. Furthermore, electrophoretic mobility shift assays revealed that H2O2 enhanced the DNA binding of AP-1 to a putative AP-1 binding element (TGAGGAA) in the p21WAF1/CIP1 promoter region (between -2203 and -2197 nucleotides upstream of the transcription initiation site). An increase in c-Jun phosphorylation by ERK was also found to accompany the increased AP-1 activity as detected by Western blot. PD98059, a specific inhibitor of MEK, diminished H2O2-induced phosphorylation of c-Jun and DNA binding activity of AP-1, decreased expression of p21WAF1/CIP1, and released the cells from G2/M arrest. Taken together, these results revealed a novel AP-1 binding site in the promoter region of p21WAF1/CIP1 and a possible cell cycle regulation mechanism mediated by activation of a redox-dependent ERK signaling pathway.

Original languageEnglish
Pages (from-to)1248-1253
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume293
Issue number4
DOIs
Publication statusPublished - 2002 Jul 4

Fingerprint

Transcription Factor AP-1
Lung Neoplasms
Chemical activation
Cells
Cell Cycle
Phosphorylation
Genetic Promoter Regions
Oxidation-Reduction
Lung
Electrophoretic mobility
Oxidative stress
MAP Kinase Signaling System
G2 Phase
Transcription Initiation Site
DNA
Mitogen-Activated Protein Kinase Kinases
Electrophoretic Mobility Shift Assay
Cell Division
Assays
Reactive Oxygen Species

Keywords

  • Activator protein-1
  • Extracellular signal regulated kinase
  • Oxidative stress
  • p21
  • Reactive oxygen species
  • Redox

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

H2O2-induced AP-1 activation and its effect on p21WAF1/CIP1-mediated G2/M arrest in a p53-deficient human lung cancer cell. / Wook Chung, Youn; Jeong, Dae won; Yun Won, Joo; Choi, Eui Ju; Hyun Choi, Yung; Kim, Ick Young.

In: Biochemical and Biophysical Research Communications, Vol. 293, No. 4, 04.07.2002, p. 1248-1253.

Research output: Contribution to journalArticle

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