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A critical role for Mnt in Myc-driven T-cell proliferation and oncogenesis

Jason M Link1, Sara Ota, Zi-Qiang Zhou

  • 1Shriners Hospitals for Children-Portland, Portland, OR 97239, USA.

Proceedings of the National Academy of Sciences of the United States of America
|November 15, 2012
PubMed

Insights

Max's next tango (Mnt) suppresses apoptosis, a role independent of Myc. Loss of Mnt leads to increased cell death, impacting Myc-driven oncogenesis and T-cell survival.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Mnt (Max's next tango) is a transcriptional repressor interacting with Max.
  • Mnt antagonizes both proliferative and apoptotic functions of Myc in vitro.
  • The in vivo functions of Mnt and its relationship with Myc remain unclear.

Purpose of the Study:

  • To define the physiological functions of Mnt in vivo.
  • To elucidate the relationship between Mnt and Myc in T-cell development and oncogenesis.
  • To investigate the role of Mnt in Myc-driven tumor formation.

Main Methods:

  • Generation of mouse strains with Mnt deletion in T cells.
  • Analysis of T-cell survival and proliferation in Mnt-deficient mice with varying c-Myc levels.
  • Assessment of Myc-induced transformation in Mnt-deficient mouse embryo fibroblasts (MEFs).
  • Investigation of reactive oxygen species (ROS) in Mnt-loss-mediated apoptosis.

Main Results:

  • Apoptosis due to Mnt loss does not require Myc.
  • Ectopic Myc expression reduces survival of Mnt-deficient T cells and MEFs.
  • Mnt absence prevents Myc-driven T-cell expansion and thymoma formation.
  • Mnt-deficient MEFs are resistant to Myc-induced oncogenic transformation.
  • Tumor suppression from Mnt loss is linked to ROS-mediated apoptosis.

Conclusions:

  • Mnt's dominant physiological role is apoptosis suppression, independent of Myc.
  • Mnt acts as a tumor suppressor by limiting Myc's oncogenic potential.
  • These findings redefine the Mnt-Myc relationship and Myc oncogenesis requirements.

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