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Inhibition of NF-Kappa B Stabilizes gadd45 Alpha mRNA

Public Domain


Details

  • Personal Author:
  • Description:
    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. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    0006-291X
  • Document Type:
    Text
  • Genre:
    Journal Article
  • Place as Subject:
  • CIO:
    National Institute for Occupational Safety and Health (NIOSH)
  • Division:
    HELD - Health Effects Laboratory Division
  • Topic:
    Workplace Safety & Health
  • Location:
    North America
  • Pages in Document:
    95-99
  • Volume:
    329
  • Issue:
    1
  • NIOSHTIC Number:
    nn:20026268
  • Citation:
    Biochem Biophys Res Commun 2005 Apr; 329(1):95-99
  • Contact Point Address:
    The Health Effects Laboratory Division, Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA
  • Email:
    LFD3@cdc.gov
  • Federal Fiscal Year:
    2005
  • Peer Reviewed:
    True
  • Source Full Name:
    Biochemical and Biophysical Research Communications
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:b82d3890403b1f37c35e2b88adfb7531fae9a03eba9cdc6f8868e8801b1f1275ef2c7fda8a4c0d5e2281203b32b7d09bd829d074238b5480b363762529d0ddba
  • Download URL:
  • File Type:
    Filetype[PDF - 315.72 KB ]
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