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.
Funding
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.
| Funders |
|---|
| Centers for Disease Control and Prevention |
Keywords
- Arsenite
- Cell cycle
- GADD45α
- JNK
- NF-κB
- p53
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research
