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Regulation of PP2A by Sphingolipid Metabolism and Signaling

Joshua Oaks1, Besim Ogretmen1

  • 1Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina , Charleston, SC , USA.

Frontiers in Oncology
|February 3, 2015
PubMed

Insights

Protein phosphatase 2A (PP2A) regulates cell proliferation and acts as a tumor suppressor. Sphingolipids may activate PP2A by targeting the SET oncoprotein, offering potential cancer therapies.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cancer Research

Background:

  • Protein phosphatase 2A (PP2A) is a key serine/threonine phosphatase regulating cellular proliferation, cell cycle, and apoptosis, thus exhibiting tumor suppressor functions.
  • PP2A activity is often inhibited in cancers through mechanisms like overexpression or modification of endogenous inhibitors, such as SET/I2PP2A.
  • Dysregulation of PP2A contributes to tumorigenesis, highlighting its importance as a therapeutic target.

Purpose of the Study:

  • To review the interactions between sphingolipids and the PP2A inhibitor SET.
  • To explore the role of these interactions in regulating PP2A activity.
  • To discuss the therapeutic potential of sphingolipids for cancer treatment by targeting SET and activating PP2A.

Main Methods:

  • Literature review of current research on PP2A, SET oncoprotein, and sphingolipids.
  • Analysis of molecular mechanisms underlying PP2A inhibition by SET.
  • Examination of studies investigating sphingolipid modulation of SET and PP2A activity.

Main Results:

  • Sphingolipids interact with the SET oncoprotein, influencing PP2A activity.
  • Modulation of SET by sphingolipids can lead to the activation of PP2A.
  • This activation of PP2A by sphingolipids demonstrates potential for tumor suppression.

Conclusions:

  • Sphingolipids represent a promising class of molecules for targeting the SET oncoprotein.
  • Targeting SET with sphingolipids can reactivate PP2A's tumor suppressor functions.
  • Sphingolipid-based therapies hold therapeutic potential for various cancers by modulating PP2A activity.
Keywords:
FTY720PP2Aceramidesphingolipidstumor suppression

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