Related Experiment Video
Updated: Aug 17, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Differential regulation of survivin by p53 contributes to cell cycle dependent apoptosis
1Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Abstract:
Recent studies indicate that cell-cycle checkpoints are tightly correlated with the regulation of apoptosis, in which p53 plays an important role. Our present works show that the expression of E6/E7 oncogenes of human papillomavirus in HeLa cells is inhibited in the presence of anti-tumor reagent tripchlorolide (TC), which results in the up-regulation of p53 in HeLa cells. Interestingly, under the same TC-treatment, the cells at the early S-phase are more susceptible to apoptosis than those at the middle S-phase although p53 protein is stabilized to the same level in both situations. Significant difference is exhibited between the two specified expression profiles. Further analysis demonstrates that anti-apoptotic gene survivin is up-regulated by p53 in the TC-treated middle-S cells, whereas it is down-regulated by p53 in the TC-treated early-S cells. Taken together, the present study indicates that the differential p53-regulated expression of survivin at different stages of the cell cycle results in different cellular outputs under the same apoptosis-inducer.
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.
Related Concept Videos
Negative Regulator Molecules
Abnormal Proliferation
DNA Damage Can Stall the Cell Cycle
DNA Damage can Stall the Cell Cycle
The Intrinsic Apoptotic Pathway
Molecular Factors Affecting Cell Division
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...

