TRIAD1 Is a Novel Transcriptional Target of p53 and Regulates Nutlin-3a-Induced Cell Death

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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Junwoo Lee1, Sungkwan An1, Yeong Min Choi1,2

  • 1Research Institute for Molecular-Targeted Drugs, Department of Biological Engineering, Konkuk University, Seoul, 05029, Republic of Korea.

Journal of Cellular Biochemistry
|December 10, 2016
PubMed

Insights

Nutlin-3a

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Nutlin-3a is an MDM2 inhibitor investigated for cancer therapy.
  • Its efficacy is not solely dependent on MDM2 levels.
  • TRIAD1's role in Nutlin-3a's anticancer effects is unexplored.

Purpose of the Study:

  • To investigate the role of TRIAD1 in regulating the anticancer activity of Nutlin-3a.
  • To elucidate the mechanism of TRIAD1-mediated regulation of p53 activation by Nutlin-3a.

Main Methods:

  • In silico analysis and promoter luciferase assays to study TRIAD1 transcription.
  • TRIAD1 silencing and overexpression in cancer cells.
  • Cell viability, cell cycle, clonogenic, and soft-agar assays to assess Nutlin-3a's effects.

Main Results:

  • Nutlin-3a enhances TRIAD1 transcription in a p53-dependent manner via a p53 consensus sequence.
  • TRIAD1 silencing suppresses Nutlin-3a-induced p53 activation and target gene expression.
  • TRIAD1 knockdown reduces Nutlin-3a's cytotoxic and growth inhibitory effects in p53 wild-type cells.

Conclusions:

  • TRIAD1 acts as a positive regulator of Nutlin-3a-mediated p53 activation.
  • TRIAD1 is crucial for the cytotoxic activity of Nutlin-3a in cancer cells.
  • This highlights a novel feedback loop involving TRIAD1 and p53 in cancer therapy.
Keywords:
APOPTOSISNUTLIN-3aTRANSCRIPTION TARGETTRIAD1p53

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