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Non-proteolytic regulation of p53-mediated transcription through destabilization of the activator.promoter complex by the proteasomal ATPases

Academic Article
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Overview

authors

  • Kim, Y. C.
  • Wu, S. Y.
  • Lim, H. S.
  • Chiang, C. M.
  • Kodadek, Thomas

publication date

  • December 2009

journal

  • Journal of Biological Chemistry  Journal

abstract

  • It has been shown previously that sub-complexes of the 26 S proteasome can regulate gene expression via non-proteolytic mechanisms. One such mechanism is the disruption of activator.promoter complexes in an ATP-dependent fashion, which was discovered in the context of the yeast Gal4 system. This activity strongly inhibits Gal4-driven gene expression unless the activator is mono-ubiquitylated, which protects it from the ATPases. To address whether this paradigm is also applicable to medically important mammalian transcriptional activators we report here a study of the interaction of the proteasomal ATPases with p53. It is shown that p53 binds directly to the ATPases via its C-terminal tetramerization and regulatory domain and that p53.promoter complexes are indeed vulnerable to ATPase-dependent disruption by the ATPase complex in vitro. Knockdown of one of the ATPases, Rpt6, in living cells results in increased occupancy of the p21(waf1) promoter by p53 and increased expression of the gene, consistent with the idea that the proteasomal ATPases negatively regulate p53 function in a non-proteolytic fashion.

subject areas

  • Adenosine Triphosphatases
  • Cell Line
  • Cyclin-Dependent Kinase Inhibitor p21
  • Humans
  • Promoter Regions, Genetic
  • Proteasome Endopeptidase Complex
  • Protein Subunits
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Transcription, Genetic
  • Transcriptional Activation
  • Tumor Suppressor Protein p53
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Identity

PubMed Central ID

  • PMC2787313

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M109.017277

PubMed ID

  • 19846554
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Additional Document Info

start page

  • 34522

end page

  • 34530

volume

  • 284

issue

  • 50

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