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 language | English |
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Pages (from-to) | 95-99 |
Number of pages | 5 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 329 |
Issue number | 1 |
DOIs | |
State | Published - Apr 1 2005 |
Keywords
- Gadd45α
- Ikkβ
- NF-κB
- Nucleolin
- mRNA stability
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology