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A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
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A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors

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Protein phosphatase 2A regulates life and death decisions via Akt in a context-dependent manner

Shaida Andrabi1, Ole V Gjoerup, Jennifer A Kean

  • 1Department of Biochemistry, Sackler School of Graduate Biomedical Sciences, School of Medicine, Tufts University, Boston, MA 02111, USA.

Proceedings of the National Academy of Sciences of the United States of America
|November 17, 2007
PubMed

Insights

Targeting protein phosphatase 2A (PP2A) influences apoptosis based on cellular signals. Polyoma small T oncoprotein modulates Akt activity via PP2A, impacting cell survival in cancer therapy strategies.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Signal Transduction

Background:

  • Protein Phosphatase 2A (PP2A) is a crucial regulator of protein phosphorylation.
  • The oncoprotein polyoma small T interacts with PP2A, influencing cellular survival pathways.
  • Akt signaling is a key mediator of cell survival and apoptosis.

Purpose of the Study:

  • To investigate how targeting PP2A affects apoptosis in cells.
  • To elucidate the role of polyoma small T and its interaction with PP2A in regulating cell survival.
  • To understand the differential regulation of Akt activity by PP2A under varying cellular conditions.

Main Methods:

  • Investigated the effects of PP2A modulation on apoptosis.
  • Utilized polyoma small T oncoprotein to interact with PP2A.
  • Analyzed Akt activation and phosphorylation patterns (T308, S473) using biochemical assays.
  • Examined substrate phosphorylation of Akt under different growth factor conditions.

Main Results:

  • PP2A targeting can induce or prevent apoptosis depending on cellular signals.
  • Polyoma small T binding to PP2A differentially regulates Akt activity.
  • In the presence of growth factors, small T induces apoptosis requiring partial Akt activation (T308 phosphorylation).
  • In the absence of growth factors, small T protects cells by promoting full Akt activation (T308 and S473 phosphorylation).

Conclusions:

  • The interaction between polyoma small T and PP2A dictates Akt's role in apoptosis.
  • Akt can function in a pro-apoptotic or anti-apoptotic manner based on its phosphorylation status, regulated by PP2A.
  • Therapeutic strategies targeting Akt phosphorylation via PP2A modulation may offer new avenues for cancer treatment.

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