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Inhibition of NF-kappa B stabilizes gadd45 alpha mRNA.

Authors
Zheng X; Zhang YD; Chen YQ; Castranova V; Shi XL; Chen F
Source
Biochem Biophys Res Commun 2005 Apr; 329(1):95-99
NIOSHTIC No.
20026268
Abstract
Growth arrest- and DNA damage-inducible protein a (gadd45alpha) is an important regulator for cell cycle, genomic stability, and cell apoptosis. In the present report, we demonstrated that NF-kappaB inhibition due to Ikkbeta deficiency enhanced the stability of gadd45alpha mNRA. Using embryo fibroblast cells derived from wild type (wt) or Ikkbeta gene knockout (Ikkbeta-/-) mice, reverse transcription-polymerase chain reaction revealed a three- to fourfold increase of gadd45alpha mRNA in Ikkbeta-/- cells compared with wt cells. The deficiency in Ikkbeta substantially decreased basal NF-kappaB activity and increased accumulation of reactive oxygen species (ROS). However, such deficiency had no effect on the basal expression or activity of Akt, FoxO3a, p53, and c-myc that regulate the transcription of gadd45alpha gene positively or negatively. Analysis of gadd45alpha mRNA stability showed a ROS-dependent increase in the half-life of gadd45alpha mRNA in Ikkbeta-/- cells. Immunoprecipitation experiments indicated an increased binding of a RNA stabilizing protein, nucleolin, to gadd45alpha mRNA in Ikkbeta-/- cells. The binding of nucleolin to gadd45alpha mRNA could be prevented by the antioxidant, N-acetyl-cysteine. Thus, these data are the first to suggest that inhibition of Ikkbeta-NF-kappaB signaling up-regulates the expression of gadd45alpha mNRA through a post-transcriptional, rather than a transcriptional, mechanism.
Keywords
Antioxidants; Antioxidation; Genetics; Genes; Gene-mutation; DNA-damage; Cell-function; Cellular-function; Cell-biology; Author Keywords: NF-jB; Ikkb; Gadd45a; mRNA stability; Nucleolin
Contact
The Health Effects Laboratory Division, Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA
CODEN
BBRCA9
Publication Date
20050401
Document Type
Journal Article
Email Address
LFD3@cdc.gov
Fiscal Year
2005
Issue of Publication
1
ISSN
0006-291X
NIOSH Division
HELD
Source Name
Biochemical and Biophysical Research Communications
State
WV
Page last reviewed: May 5, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division