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Nucleolin links to arsenic-induced stabilization of GADD5alpha mRNA.

Authors
Zhang-Y; Bhatia-D; Xia-H; Castranova-V; Shi-X; Chen-F
Source
Nucleic Acids Res 2006 Jan; 34(2):485-495
NIOSHTIC No.
20029267
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+.
Keywords
Nucleic-acids; Arsenic-compounds; DNA-damage; Genes; Nucleic-acid-repair; Nucleic-acid-metabolism
Contact
PPRB/NIOSH, Room L2015, 1095 Willowdale Road, Morgantown, WV 26505, USA
CODEN
NARHAD
Publication Date
20060118
Document Type
Journal Article
Email Address
lfd3@cdc.gov
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0305-1048
NIOSH Division
HELD
Source Name
Nucleic Acids Research
State
WV
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