The p53-p21-DREAM-CDE/CHR pathway regulates G2/M cell cycle genes

Martin Fischer1, Marianne Quaas1, Lydia Steiner2

  • 1Molecular Oncology, Medical School, University of Leipzig, Leipzig, Germany.

Nucleic Acids Research
|September 20, 2015
PubMed

Insights

The tumor suppressor p53 regulates cell cycle genes via the p53-p21-DREAM-CDE/CHR pathway. This pathway is a key mechanism for p53-induced G2/M cell cycle arrest.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The tumor suppressor p53 is a transcription factor controlling cell cycle arrest and apoptosis.
  • p53 indirectly represses cell cycle genes (e.g., CCNB2, KIF23, PLK4) via the p53-p21-DREAM-CDE/CHR pathway.
  • The prevalence of this regulatory pathway remained largely uncharacterized.

Purpose of the Study:

  • To identify genes regulated by p53 through the p53-p21-DREAM-CDE/CHR pathway on a genome-wide scale.
  • To determine if this pathway is a principal mechanism for p53-mediated G2/M cell cycle arrest.

Main Methods:

  • Genome-wide computational analysis integrating DREAM complex binding data, p53-dependent mRNA expression data, and conserved CHR promoter elements.
  • Bioinformatic identification of potential target genes.
  • Experimental validation of p53-dependent repression for specific cell cycle genes (e.g., MYBL2, BUB1, CCNA2).

Main Results:

  • Identified 210 target genes regulated by the p53-p21-DREAM-CDE/CHR pathway.
  • Confirmed p53-dependent repression of key cell cycle genes including MYBL2, BUB1, CCNA2, CCNB1, CHEK2, MELK, POLD1, RAD18, and RAD54L.
  • The majority of the 210 identified genes are critical for G2 phase and mitosis regulation.

Conclusions:

  • The p53-p21-DREAM-CDE/CHR pathway is a significant mechanism by which p53 regulates gene expression.
  • Downregulation of essential G2/M regulators via this pathway is a principal mechanism for p53-induced G2/M cell cycle arrest.

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