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A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
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Proteome analysis revealed the essential functions of protein phosphatase PP2A in the induction of Th9 cells

Suyasha Roy1, Renu Goel2, Suruchi Aggarwal2

  • 1Immuno-Biology Laboratory, Translational Health Science and Technology Institute (THSTI), 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad, Haryana, 121 001, India.

Scientific Reports
|July 5, 2020
PubMed

Insights

Protein phosphatase 2A (PP2A) is crucial for the development and anti-tumor activity of Th9 cells. Inhibiting PP2A impairs Th9 cell function and anti-tumor immunity, highlighting its essential role.

Area of Science:

  • Immunology
  • Proteomics
  • Cell Biology

Background:

  • Th9 cells play a critical role in anti-tumor immunity.
  • Post-translational protein modifications are vital for cellular functions but often overlooked in transcriptomic studies.
  • The specific role of protein phosphatase 2A (PP2A) in Th9 cell differentiation and function remains unclear.

Purpose of the Study:

  • To investigate the proteomic landscape of Th9 cells.
  • To identify proteins enriched in Th9 cells that contribute to their anti-tumor functions.
  • To elucidate the role of PP2A in Th9 cell differentiation and anti-tumor immunity.

Main Methods:

  • Comprehensive proteomic analysis of murine Th0 and Th9 cells.
  • Pathway analysis to identify enriched protein classes, particularly phosphoproteins.
  • Inhibition of PP2A activity to assess its impact on Th9 cell differentiation and function.
  • Evaluation of Th9 cell-mediated anti-tumor immune response in a B16-OVA melanoma model.

Main Results:

  • Proteomic analysis revealed proteins enriched in Th9 cells compared to Th0 cells.
  • Th9 cells showed an abundance of phosphoproteins, with Ppp2ca (catalytic subunit of PP2A) being highly enriched.
  • PP2A inhibition suppressed Interleukin-9 (IL-9) production and key transcription factor expression in Th9 cells.
  • Inhibition of PP2A abrogated Th9 cell-mediated anti-tumor immune responses in a melanoma model.

Conclusions:

  • PP2A is essential for the proper differentiation of Th9 cells.
  • PP2A plays a critical role in mediating the anti-tumor immune functions of Th9 cells.
  • Targeting PP2A may offer a therapeutic strategy to enhance anti-tumor immunity.

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