Differential regulation of survivin by p53 contributes to cell cycle dependent apoptosis

Yan Jin1, Yong Wei, Lei Xiong

  • 1Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Cell Research
|May 27, 2005
PubMed

Insights

Tripchlorolide (TC) up-regulates p53 in HeLa cells, affecting apoptosis differently based on cell cycle stage. p53 differentially regulates survivin, influencing cell death susceptibility during early versus middle S-phase.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Cell-cycle checkpoints and apoptosis are crucial in regulating cell fate.
  • The p53 tumor suppressor protein plays a significant role in both processes.
  • Human papillomavirus (HPV) oncoproteins E6/E7 can disrupt normal cell cycle control and apoptosis.

Purpose of the Study:

  • To investigate the effect of the anti-tumor reagent tripchlorolide (TC) on HPV-infected HeLa cells.
  • To elucidate the role of p53 and its regulation of downstream genes, such as survivin, in response to TC treatment at different cell cycle phases.

Main Methods:

  • Treatment of HeLa cells with tripchlorolide (TC).
  • Analysis of p53 expression and stabilization.
  • Assessment of apoptosis susceptibility at different cell cycle stages (early vs. middle S-phase).
  • Investigation of survivin gene expression regulated by p53.

Main Results:

  • TC inhibited HPV E6/E7 oncogene expression and up-regulated p53 in HeLa cells.
  • Cells in early S-phase were more susceptible to apoptosis than middle S-phase cells upon TC treatment, despite similar p53 stabilization.
  • p53 up-regulated survivin in middle S-phase cells but down-regulated it in early S-phase cells.

Conclusions:

  • The differential regulation of survivin by p53 at distinct cell cycle phases leads to varied cellular responses to apoptosis inducers.
  • Cell cycle stage-specific modulation of gene expression by p53 is a critical determinant of apoptosis outcome.

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