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The c-Myc target gene PRDX3 is required for mitochondrial homeostasis and neoplastic transformation

Diane R Wonsey1, Karen I Zeller, Chi V Dang

  • 1Program in Human Genetics and Molecular Biology and Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 16, 2002
PubMed

Insights

This study identifies PRDX3 as a novel nuclear c-Myc target gene crucial for mitochondrial function. PRDX3 supports cancer cell proliferation and survival by maintaining mitochondrial integrity.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Mitochondrial Biology

Background:

  • Deregulated c-Myc is implicated in numerous human cancers.
  • c-Myc exerts its oncogenic effects primarily through transcriptional regulation of target genes.
  • The role of c-Myc in regulating mitochondrial function is not fully understood.

Purpose of the Study:

  • To identify and characterize novel c-Myc target genes involved in mitochondrial function.
  • To elucidate the role of PRDX3, a peroxiredoxin family member, as a c-Myc target gene.
  • To investigate the impact of PRDX3 on mitochondrial homeostasis and cancer cell phenotypes.

Main Methods:

  • Utilized the mycER system and c-myc(-/-) cells to study PRDX3 expression.
  • Performed chromatin immunoprecipitation (ChIP) to identify Myc binding sites on the PRDX3 gene.
  • Employed mitochondria-specific fluorescent probes to assess mitochondrial function.

Main Results:

  • PRDX3 expression is induced by Myc and reduced in c-myc deficient cells.
  • Myc binds to a specific region of the PRDX3 genomic locus.
  • PRDX3 is essential for Myc-mediated proliferation, transformation, and resistance to glucose withdrawal.
  • PRDX3 maintains mitochondrial mass and membrane potential in cancer cells.

Conclusions:

  • PRDX3 is a direct nuclear c-Myc target gene.
  • PRDX3 plays a critical role in maintaining mitochondrial function in cancer cells.
  • Targeting PRDX3 may offer a therapeutic strategy for c-Myc-driven cancers.

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