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Immunofluorescence Analysis of Stress Granule Formation After Bacterial Challenge of Mammalian Cells
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The PI3K and MAPK/p38 pathways control stress granule assembly in a hierarchical manner

Alexander Martin Heberle1, Patricia Razquin Navas1,2, Miriam Langelaar-Makkinje1

  • 1Laboratory of Pediatrics, Section Systems Medicine of Metabolism and Signaling, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Life Science Alliance
|March 30, 2019
PubMed

Insights

Cells use stress granules for survival. This study reveals PI3K and p38 kinases hierarchically promote stress granule formation via mTORC1, highlighting a potential cancer vulnerability.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Stress Response Mechanisms

Background:

  • Cells possess stress-coping mechanisms for survival.
  • Stress granules, cytoplasmic protein-RNA assemblies, are crucial for cellular survival under stress.
  • Stress granules represent a poorly explored tumor vulnerability.

Purpose of the Study:

  • To identify novel regulators of stress granule assembly.
  • To investigate the role of PI3K and MAPK/p38 kinases in stress granule formation.
  • To elucidate the signaling pathways governing stress granule assembly in cancer.

Main Methods:

  • Systems biology approach to identify kinases involved in stress granule assembly.
  • Analysis of signaling pathways including PI3K, MAPK/p38, and mTORC1.
  • Examination of signaling hierarchy in human breast cancer tissue.

Main Results:

  • PI3K and MAPK/p38 (p38) were identified as pro-stress-granule-kinases.
  • These kinases promote stress granule assembly through mammalian target of rapamycin complex 1 (mTORC1).
  • A hierarchical activation of PI3K and p38 regulates stress granule formation, a hierarchy also observed in breast cancer.

Conclusions:

  • PI3K and p38 kinases have a novel pro-survival function in promoting stress granule formation.
  • The hierarchical signaling of PI3K and p38 is critical for stress granule assembly.
  • Understanding this pathway offers new insights into targeting tumor vulnerabilities.

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