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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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ZAS3 represses NFκB-dependent transcription by direct competition for DNA binding

  • Hong, Joung-Woo (The Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Wu, Lai-Chu (Department Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University)
  • Received : 2010.11.02
  • Accepted : 2010.11.06
  • Published : 2010.12.31
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Abstract

$NF{\kappa}B$ and ZAS3 are transcription factors that control important cellular processes including immunity, cell survival and apoptosis. Although both proteins bind the ${\kappa}B$-motif, they produce opposite physiological consequences; $NF{\kappa}B$ activates transcription, promotes cell growth and is often found to be constitutively expressed in cancer cells, while ZAS3 generally represses transcription, inhibits cell proliferation and is downregulated in some cancers. Here, we show that ZAS3 inhibits $NF{\kappa}B$-dependent transcription by competing with $NF{\kappa}B$ for the ${\kappa}B$-motif. Transient transfection studies show that N-terminal 645 amino acids is sufficient to repress transcription activated by $NF{\kappa}B$, and that the identical region also possesses intrinsic repression activity to inhibit basal transcription from a promoter. Finally, in vitro DNA-protein interaction analysis shows that ZAS3 is able to displace $NF{\kappa}B$ by competing with $NF{\kappa}B$ for the ${\kappa}B$-motif. It is conceivable that ZAS3 has therapeutic potential for controlling aberrant activation of $NF{\kappa}B$ in various diseases.

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References

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