Inhibition of NF-κB stabilizes gadd45α mRNA

Xue Zheng, Yadong Zhang, Yu Quan Chen, Vince Castranova, Xianglin Shi, Fei Chen

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Growth arrest- and DNA damage-inducible protein α (gadd45α) is an important regulator for cell cycle, genomic stability, and cell apoptosis. In the present report, we demonstrated that NF-κB inhibition due to Ikkβ deficiency enhanced the stability of gadd45α mNRA. Using embryo fibroblast cells derived from wild type (wt) or Ikkβ gene knockout (Ikkβ-/-) mice, reverse transcription-polymerase chain reaction revealed a three- to fourfold increase of gadd45α mRNA in Ikkβ-/- cells compared with wt cells. The deficiency in Ikkβ substantially decreased basal NF-κB 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 gadd45α gene positively or negatively. Analysis of gadd45α mRNA stability showed a ROS-dependent increase in the half-life of gadd45α mRNA in Ikkβ-/- cells. Immunoprecipitation experiments indicated an increased binding of a RNA stabilizing protein, nucleolin, to gadd45α mRNA in Ikkβ-/- cells. The binding of nucleolin to gadd45α mRNA could be prevented by the antioxidant, N-acetyl-cysteine. Thus, these data are the first to suggest that inhibition of Ikkβ-NF-κB signaling up-regulates the expression of gadd45α mNRA through a post-transcriptional, rather than a transcriptional, mechanism.

Original languageEnglish
Pages (from-to)95-99
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume329
Issue number1
DOIs
StatePublished - Apr 1 2005

Keywords

  • Gadd45α
  • Ikkβ
  • NF-κB
  • Nucleolin
  • mRNA stability

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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