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

Oncogene volume 20, pages 3585–3589 (2001)Cite this article

Abstract

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 IκB 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.

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Acknowledgements

We are grateful to Dr Hiroyasu Nakano (Juntendo University, Japan) for providing pCR-Flag-IKKβ and pCR-Flag-IKKβ-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.

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  1. The Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, 26505, West Virginia, WV, USA

    Fei Chen, Zhou Zhang, Stephen S Leonard & Xianglin Shi

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Chen, F., Zhang, Z., Leonard, S. et al. Contrasting roles of NF-κB and JNK in arsenite-induced p53-independent expression of GADD45α. Oncogene 20, 3585–3589 (2001). https://doi.org/10.1038/sj.onc.1204442

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