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Updated: May 21, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Rewiring drug-activated p53-regulatory network from suppressing to promoting tumorigenesis

Wei Song1, Jiguang Wang, Ying Yang

  • 1Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

Journal of Molecular Cell Biology
|June 5, 2012
PubMed

Insights

The chemotherapeutic agent 5-aza-2'-deoxycytidine (ZdCyd) differentially affects mouse P19 cell tumorigenicity. ZdCyd suppresses attached cells but promotes suspended cells, with context-dependent p53 network roles in cancer development.

Area of Science:

  • Cancer Biology
  • Molecular Oncology
  • Epigenetics

Background:

  • Oncogenes and tumor suppressor genes can have opposing roles depending on tumor type and stage.
  • The chemotherapeutic agent 5-aza-2 '-deoxycytidine (ZdCyd) is a DNA methyltransferase inhibitor.

Purpose of the Study:

  • To investigate the context-dependent effects of ZdCyd on P19 cell tumorigenicity.
  • To elucidate the role of p53 in ZdCyd-mediated alterations of P19 cell behavior.

Main Methods:

  • Treatment of P19 cells (attached and detached) with ZdCyd.
  • Analysis of p53 activity and gene expression profiles.
  • Computational approaches to analyze gene-regulatory and protein-protein interaction networks.
  • siRNA-mediated inhibition of p53.

Main Results:

  • ZdCyd suppressed tumorigenicity in attached P19 cells but enhanced it in detached P19 cells.
  • p53 activity was upregulated by ZdCyd in both conditions.
  • Apoptotic pathways were enriched in attached cells, while pro-survival pathways were enriched in detached cells.
  • ZdCyd-activated p53 exhibited oncogenic function in detached P19 cells.

Conclusions:

  • The p53-dominant network activated by ZdCyd plays context-dependent roles in tumorigenesis.
  • These findings highlight the complex, condition-specific functions of p53 in cancer.

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