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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

Pag, a putative tumor suppressor, interacts with the Myc Box II domain of c-Myc and selectively alters its biological

Zhao Mei Mu1, Xiao Ying Yin, Edward V Prochownik

  • 1Section of Hematology/Oncology, The Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.

The Journal of Biological Chemistry
|August 28, 2002
PubMed

Insights

Pag protein interacts with c-Myc's MBII domain, influencing cell growth, apoptosis, and oxidative stress resistance. While mimicking some c-Myc functions, Pag also inhibits c-Myc-driven tumorigenesis and gene regulation, suggesting a tumor suppressor role.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The Myc Box II (MBII) domain of c-Myc is crucial for its oncogenic functions.
  • Pag, a peroxiredoxin family member, interacts with c-Abl and influences cell proliferation.
  • The functional relationship between Pag and c-Myc remains largely unexplored.

Purpose of the Study:

  • To investigate the interaction between Pag and the c-Myc MBII domain.
  • To elucidate Pag's role in c-Myc-mediated cellular processes, including transformation, apoptosis, and oxidative stress response.
  • To determine Pag's impact on c-Myc-driven tumorigenesis and gene regulation.

Main Methods:

  • Yeast two-hybrid screening to identify MBII-interacting proteins.
  • Cell-based assays to assess Pag's effects on cell size, apoptosis, and oxidative stress.
  • Tumorigenesis assays using c-Myc-overexpressing fibroblasts.
  • Analysis of c-Myc target gene regulation.

Main Results:

  • Pag directly interacts with the c-Myc MBII domain.
  • Pag promotes cell enlargement and apoptosis, mimicking ectopic c-Myc overexpression.
  • Pag confers resistance to oxidative stress in conjunction with c-Myc.
  • Pag inhibits c-Myc-driven fibroblast tumorigenesis and selectively impairs c-Myc target gene regulation.

Conclusions:

  • Pag modulates c-Myc activity, exhibiting both synergistic and antagonistic effects.
  • Pag's dual role in promoting certain c-Myc phenotypes while inhibiting others, alongside its interaction with c-Abl, supports its function as a tumor suppressor.

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