Contrasting Roles of NF-kB and JNK in Arsenite-Induced p53-Independent Expression of GADD45alpha

Details

• Personal Author:
  Chen F ; Leonard, Stephen S. ; Shi X ; Zhang Z
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Carcinogens Occupational Health Safety
• Keywords:
  Arsenites Author Keywords: Arsenite Cell Cycle GADD45a JNK NFkB P53
• ISSN:
  0950-9232
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  20
• Issue:
  27
• NIOSHTIC Number:
  nn:20021700
• Citation:
  Oncogene 2001 Jun; 20(27):3585-3589
• Contact Point Address:
  F Chen, The Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, West Virginia, WV 26505, USA
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  True
• Source Full Name:
  Oncogene
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:aefc934a021ba3ee45a8a0dc9c0cf9fa62dff9ab3162460f0231bccb9cca72d8b9ce930e0206890a191f4865198e02e1cd84b6a8f67a176bd90bf23bcea57ab4
• Download URL:
  https://stacks.cdc.gov/view/cdc/198816/cdc_198816_DS1.pdf
• File Type:
  [PDF - 354.64 KB ]