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 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 language | English |
|---|---|
| Pages (from-to) | 3585-3589 |
| Number of pages | 5 |
| Journal | Oncogene |
| Volume | 20 |
| Issue number | 27 |
| DOIs | |
| State | Published - 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.
Keywords
- Arsenite
- Cell cycle
- GADD45α
- JNK
- NF-κB
- p53
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research
