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Contrasting roles of NF-kB and JNK in arsenite-induced p53-independent expression of GADD45alpha.

Authors
Chen-F; Zhang-Z; Leonard-SS; Shi-X
Source
Oncogene 2001 Jun; 20(27):3585-3589
NIOSHTIC No.
20021700
Abstract
Growth arrest and DNA damage-inducible protein 45alpha (GADD45alpha) 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 GADD45alpha expression in a p53-independent fashion and that this GADD45alpha induction by arsenite is regulated by NF-kappaB and c-Jun-N-terminal kinase (JNK) oppositely. In human bronchial epithelial cells overexpressing a kinase-mutated form of IkappaB kinase beta (IKKbeta-KM), the activation of NF-kappaB was inhibited. However, the G2/M cell cycle arrest and expression of GADD45alpha 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 GADD45alpha expression. Analysis of GADD45alpha expression in both wild-type and p53-/- fibroblasts indicated that the induction of GADD45alpha by arsenite was independent of the status of p53 protein.
Keywords
Arsenites; Carcinogens
Contact
F Chen, The Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, West Virginia, WV 26505, USA
CODEN
ONCNES
Publication Date
20010614
Document Type
Journal Article
Fiscal Year
2001
NTIS Accession No.
NTIS Price
Issue of Publication
27
ISSN
0950-9232
NIOSH Division
HELD
Source Name
Oncogene
State
WV
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