Contrasting roles of NF-κB and JNK in arsenite-induced p53-independent expression of GADD45α

F. Chen, Z. Zhang, S. S. Leonard, X. Shi

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Growth arrest and DNA damage-inducible protein 45α (GADD45α) is an important cell cycle checkpoint protein that arrests cells at G2/M phase by inhibiting the activity of G2-specific kinase, cyclin B/p34cdc2. We report here that arsenite induces GADD45α expression in a p53-independent fashion and that this GADD45α induction by arsenite is regulated by NF-κB and c-Jun-N-terminal kinase (JNK) oppositely. In human bronchial epithelial cells overexpressing a kinase-mutated form of IkB kinase β (IKKβ-KM), the activation of NF-κB was inhibited. However, the G2/M cell cycle arrest and expression of GADD45α was substantially enhanced in response to arsenite in these cells. Expression of a dominant-negative mutant of SEK1 that blocks JNK activation decreased arsenite-induced GADD45α expression. Analysis of GADD45α expression in both wild-type and p53-/- fibroblasts indicated that the induction of GADD45α by arsenite was independent of the status of p53 protein.

Original languageEnglish
Pages (from-to)3585-3589
Number of pages5
Issue number27
StatePublished - Jun 14 2001

Bibliographical note

Funding Information:
We are grateful to Dr Hiroyasu Nakano (Juntendo University, Japan) for providing pCR-Flag-IKKb and pCR-Flag-IKKb-KM (K44A) expressing vectors; to Dr Roger Davis (University of Massachusetts, Boston, MA, USA) for his gift of pcDNA-SEK1-KM vector; and to Drs Murali Rao, Val Vallyathan and Vince Castranova (NIOSH) for their critical reading of this manuscript. Fei Chen is supported by a Career Development Award under a cooperative agreement from the Centers for Disease Control and Prevention through the Association of Teachers of Preventive Medicine.


  • Arsenite
  • Cell cycle
  • GADD45α
  • JNK
  • NF-κB
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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