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Updated: Jul 4, 2026

Development and Application of Rapamycin-regulated Tyrosine Phosphatases
06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Protein phosphatase 2A and rapamycin regulate the nuclear localization and activity of the transcription factor GLI3

Sybille Krauss1, John Foerster, Rainer Schneider

  • 1Charité University Hospital, Department of Dermatology and Max-Planck Institute for Molecular Genetics, Berlin, Germany.

Cancer Research
|June 19, 2008
PubMed

Insights

Protein phosphatase 2A (PP2A) and rapamycin regulate GLI3, a key protein in the sonic hedgehog (SHH) pathway. This interaction impacts cell growth and offers new insights into cancer therapy targeting the SHH pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Gain-of-function alterations in the sonic hedgehog (SHH) signaling pathway are implicated in various cancers.
  • GLI1, GLI2, and GLI3 are key effectors of the SHH pathway, controlling genes involved in cell growth and proliferation.

Purpose of the Study:

  • To investigate the role of protein phosphatase 2A (PP2A) and rapamycin in regulating the nuclear localization and transcriptional activity of GLI3.
  • To elucidate the molecular cross-talk between the SHH pathway and PP2A.

Main Methods:

  • Assessed the effect of PP2A activity modulation and rapamycin treatment on GLI3 localization and transcriptional activity.
  • Quantified the expression of GLI3 target genes, including cyclin D1.

Main Results:

  • Increased PP2A activity or rapamycin treatment resulted in cytosolic retention of GLI3.
  • This retention led to reduced transcription of GLI3 target genes, such as cyclin D1.
  • Inhibition of PP2A caused increased cyclin D1 expression.

Conclusions:

  • Identified a novel molecular cross-talk between the oncogenic SHH pathway and the tumor suppressor PP2A.
  • Demonstrated a new mechanism for the anticancerogenic effects of rapamycin involving the SHH pathway and GLI3 regulation.

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