Regulation of the gadd45beta promoter by NF-kappaB

DNA Cell Biol. 2002 Jul;21(7):491-503. doi: 10.1089/104454902320219059.


In addition to coordinating immune and inflammatory responses, NF-kappaB/Rel transcription factors control cell survival. The NF-kappaB antiapoptotic function is crucial to oncogenesis, cancer chemoresistance, and to antagonize tumor necrosis factor (TNF) receptor-induced killing. Recently, we have shown that the suppression of the c-Jun-N-terminal kinase (JNK) cascade is a pivotal protective mechanism by NF-kappaB, and that this suppression involves the upregulation of gadd45beta/myd118. Induction of gadd45beta by stress and cytokines requires NF-kappaB; however, the regulatory mechanisms underlying this induction are not known. Here, we report that, in HeLa cells, the NF-kappaB subunit RelA is sufficient to activate gadd45beta expression, whereas Rel and p50 are not. Activation of gadd45beta by RelA depends on three kappaB elements at positions -447/-438 (kappaB-1), -426/-417 (kappaB-2), and -377/-368 (kappaB-3) of the gadd45beta promoter. Each of these sites binds to NF-kappaB complexes in vitro, and is required for optimal promoter transactivation. The data establish the direct participation of NF-kappaB in the regulation of Gadd45beta, thereby providing important mechanistic insights into the control of apoptosis by the transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation / genetics*
  • Apoptosis / genetics
  • Apoptosis / physiology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Chromosomes, Artificial, Bacterial / genetics
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Ligases / genetics
  • Ligases / metabolism
  • Mice
  • Molecular Sequence Data
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Plasmids / genetics
  • Promoter Regions, Genetic*
  • Transcriptional Activation
  • Up-Regulation


  • Antigens, Differentiation
  • GADD45B protein, human
  • Gadd45b protein, mouse
  • NF-kappa B
  • Ligases
  • guanosine 3',5'-polyphosphate synthetases