Nucleolin Links to Arsenic-Induced Stabilization of GADD5alpha mRNA

Details

• Personal Author:
  Bhatia D ; Castranova, Vincent ; Chen F ; Shi X ; Xia H ; Zhang Y
• Description:
  The present study shows that arsenic induces GADD45alpha (growth arrest and DNA damage inducible gene 45alpha) mainly through post-transcriptional mechanism. Treatment of the human bronchial epithelial cell line, BEAS-2B, with arsenic(III) chloride (As3+) resulted in a significant increase in GADD45alpha protein and mRNA. However, As3+ only exhibited a marginal effect on the transcription of the GADD45alpha gene. The accumulation of GADD45alpha mRNA is largely achieved by the stabilization of GADD45alpha mRNA in the cellular response to As3+. As3+ is able to induce binding of mRNA stabilizing proteins, nucleolin and less potently, HuR, to the GADD45alpha mRNA. Although As3+ was unable to affect the expression of nucleolin, treatment of the cells with As3+ resulted in re-distribution of nucleolin from nucleoli to nucleoplasm. Silencing of the nucleolin mRNA by RNA interference reversed As3+-induced stabilization of the GADD45alpha mRNA and accumulation of the GADD45alpha protein. Stabilization of GADD45alpha mRNA, thus, represents a novel mechanism contributing to the production of GADD45alpha and cell cycle arrest in response to As3+. [Description provided by NIOSH]
• Subjects:
  Arsenic DNA Genetics Inorganic Chemicals Occupational Health Safety
• Keywords:
  Arsenic-compounds DNA-damage Genes Nucleic-acid-metabolism Nucleic-acid-repair Nucleic-acids
• ISSN:
  0305-1048
• 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
• Pages in Document:
  485-495
• Volume:
  34
• Issue:
  2
• NIOSHTIC Number:
  nn:20029267
• Citation:
  Nucleic Acids Res 2006 Jan; 34(2):485-495
• Contact Point Address:
  PPRB/NIOSH, Room L2015, 1095 Willowdale Road, Morgantown, WV 26505, USA
• Email:
  lfd3@cdc.gov
• Federal Fiscal Year:
  2006
• Peer Reviewed:
  True
• Source Full Name:
  Nucleic Acids Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c8c2b7f588fff8aa40baeb73ec181633711f274726a6b6e44300a62ca170c97b5f2ac0a53564d487f9f8c1489b58be8ca2981cf30e23191875961d990ddd9f34
• Download URL:
  https://stacks.cdc.gov/view/cdc/190295/cdc_190295_DS1.pdf
• File Type:
  [PDF - 1.71 MB ]