Nucleolin links to arsenic-induced stabilization of GADD45alpha mRNA

Nucleic Acids Res. 2006 Jan 18;34(2):485-95. doi: 10.1093/nar/gkj459. Print 2006.

Abstract

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+.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Arsenicals / pharmacology*
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Chlorides / pharmacology*
  • Gene Silencing
  • Humans
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Phosphoproteins / antagonists & inhibitors
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • RNA Stability / drug effects*
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Transcription, Genetic / drug effects

Substances

  • Arsenicals
  • Cell Cycle Proteins
  • Chlorides
  • GADD45A protein, human
  • Nuclear Proteins
  • Phosphoproteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • nucleolin
  • arsenic trichloride
  • Proto-Oncogene Proteins c-akt