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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Published on: September 20, 2018

Transcriptional repression of p21((Waf1/Cip1/Sdi1)) gene by c-jun through Sp1 site

C H Wang1, Y P Tsao, H J Chen

  • 1Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China.

Biochemical and Biophysical Research Communications
|March 29, 2000
PubMed

Insights

c-Jun oncogene represses tumor suppressor p21 gene expression by targeting Sp1-3 sites in the promoter. This involves transcription factors Sp1/Sp3 and potentially hyperphosphorylated retinoblastoma protein (Rb).

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • c-Jun is known to repress the tumor suppressor p21 gene.
  • Understanding the precise mechanism of this repression is crucial for cancer research.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which c-Jun inhibits p21 gene expression.
  • To identify key regulatory elements and factors involved in c-Jun-mediated p21 repression.

Main Methods:

  • Analysis of p21 promoter deletion and point mutants.
  • Electrophoretic mobility shift assays (EMSA).
  • Investigation of transcription factors Sp1, Sp3, and retinoblastoma protein (Rb).

Main Results:

  • The Sp1-3 site (-77 and -83) of the p21 promoter is critical for c-Jun-mediated repression.
  • Sp1 and Sp3 transcription factors are key players, but c-Jun does not alter Sp1 DNA-binding affinity.
  • c-Jun inhibits butyrate-induced p21 expression via Sp1, and hyperphosphorylated Rb increases in c-Jun expressing cells, suggesting a role in Sp1-mediated p21 repression.

Conclusions:

  • c-Jun represses p21 expression through specific promoter sites involving Sp1/Sp3 transcription factors.
  • The retinoblastoma protein (Rb) may mediate c-Jun's repression of p21 via Sp1.
  • This study reveals a novel mechanism where oncogene products counteract tumor suppressor gene function to control cell cycle progression.

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