Opposite effect of NF-kappa B and c-Jun N-terminal kinase on p53-independent GADD45 induction by arsenite

Citation
F. Chen et al., Opposite effect of NF-kappa B and c-Jun N-terminal kinase on p53-independent GADD45 induction by arsenite, J BIOL CHEM, 276(14), 2001, pp. 11414-11419
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
276
Issue
14
Year of publication
2001
Pages
11414 - 11419
Database
ISI
SICI code
0021-9258(20010406)276:14<11414:OEONBA>2.0.ZU;2-E
Abstract
Cell cycle checkpoint, a major genomic surveillance mechanism,is an importa nt step in maintaining genomic stability and integrity in response to envir onmental stresses. Using cells derived from human bronchial epithelial cell s, we demonstrate that NF-kappaB and c-Jun N-terminal kinase (JNK) reciproc ally regulate arsenic trioxide (arsenite)-induced, p53-independent expressi on of GADD45 protein, a cell cycle checkpoint protein that arrests cells at the G(2)/M phase transition. Inhibition of NF-kappaB activation by stable expression of a kinase-mutated form of I kappaB kinase caused increased and prolonged induction of GADD45 by arsenite. In contrast, the induction of G ADD45 by arsenite was transient and less potent in cells where the NF-kappa B activation pathway was normal. Analysis of the cell cycle profile by flow cytometry indicated that NF-kappaB inhibition potentiates arsenite-induced G(2)/M cell cycle arrest. Abrogation of JNK activation, on the other hand, decreased GADD45 expression induced by arsenite, suggesting a role for JNK activation in GADD45 induction. These results indicate a molecular mechani sm by which NF-kappaB and JNK may differentially contribute to cell cycle r egulation in response to arsenite.