The oncoprotein Myc controls the phosphorylation of S6 kinase and AKT through protein phosphatase 2A

Lidia Chellini1,2, Valentina Monteleone1, Malinska Lombari1

  • 1Department of Biology, University of Rome Tor Vergata, Rome, Italy.

Insights

The Myc oncoprotein boosts protein synthesis by increasing 4E-binding protein 1 (4E-BP1) phosphorylation. Unexpectedly, Myc also decreases S6 kinase and AKT phosphorylation, mediated by protein phosphatase 2A activity.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • The Myc oncoprotein, frequently activated in cancer, regulates cellular processes.
  • Myc influences protein synthesis, a key energy-consuming cellular activity.
  • Myc can affect translation transcriptionally (e.g., eIF4F complex) and post-translationally (e.g., mTOR-dependent 4E-BP1 phosphorylation).

Purpose of the Study:

  • To investigate the precise effects of Myc oncoprotein on the cell's translational apparatus.
  • To elucidate the post-translational mechanisms underlying Myc-mediated translational control.

Main Methods:

  • Overexpression and inhibition of Myc using cDNA constructs and small interfering RNA (siRNA).
  • Experiments conducted in PC3 (prostate carcinoma) and HeLa (cervical carcinoma) cell lines.
  • Analysis of protein phosphorylation levels (4E-BP1, S6 kinase, AKT) and protein synthesis activity.

Main Results:

  • Myc overexpression increased 4E-binding protein 1 (4E-BP1) phosphorylation and overall protein synthesis.
  • Concurrently, Myc overexpression led to decreased phosphorylation of S6 kinase and AKT in tested cell lines.
  • Evidence suggests these effects are mediated by enhanced protein phosphatase 2A (PP2A) activity.

Conclusions:

  • Myc oncogene impacts protein synthesis through complex post-translational modifications.
  • The observed decrease in S6 kinase and AKT phosphorylation by Myc is mediated by increased PP2A activity.
  • This study reveals novel regulatory roles of Myc in cellular translation beyond transcriptional control.

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