Contrasting roles of NF-kappa B and JNK in arsenite-induced p53-independent expression of GADD45 alpha

Chen, F Zhang, Z Leonard, SS Shi, XL

F. Chen et al., Contrasting roles of NF-kappa B and JNK in arsenite-induced p53-independent expression of GADD45 alpha, ONCOGENE, 20(27), 2001, pp. 3585-3589

36

INGLESE

Article

Onconogenesis & Cancer Research

ONCOGENE

0950-9232 → ACNP

20

27

2001

3585 - 3589

ISI

0950-9232(20010614)20:27<3585:CRONBA>2.0.ZU;2-Q

Growth arrest and DNA damage-inducible protein 45 alpha (GADD45 alpha) is a n important cell cycle checkpoint protein that arrests cells at G2/M phase by inhibiting the activity of G2-specific kinase, cyclin B/p34cdc2. We repo rt here that arsenite induces GADD45 alpha expression in a p53-independent fashion and that this GADD45a induction by arsenite is regulated by NF-KB a nd c-Jun-N-terminal kinase (JNK) oppositely. In human bronchial epithelial cells overexpressing a kinase-mutated form of I kappaB kinase beta (IKK bet a -KM), the activation of NF-kappaB was inhibited. However, the G2/M cell c ycle arrest and expression of GADB45 alpha was substantially enhanced in re sponse to arsenite in these cells. Expression of a dominant-negative mutant of SEK1 that blocks JNK activation decreased arsenite-induced GADD45a expr ession. Analysis of GADD45 alpha expression in both wild-type and p53-/- fi broblasts indicated that the induction of GADD45a by arsenite was independe nt of the status of p53 protein.