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

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52 Citations (Scopus)


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
Issue number4
Publication statusPublished - 2002

Bibliographical note

Funding Information:
We thank Dr. A.J. Levine (Princeton University, USA) for generous gifts of p53 wild-type plasmid pC53-SN3. This work was supported by a grant from the Ministry of Health and Welfare, HMP-98-13-3-0017 to I.Y. Kim. This work was also partially supported by a grant from Korea University to I.Y. Kim.


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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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