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Identification of Raptor and GLI1 as USP37 substrates highlight its context-specific function in medulloblastoma

Ashutosh Singh1, Donghang Cheng1, Amanda R Haltom1

  • 1Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Oncogene
|December 17, 2025
PubMed
Summary

The USP37 gene has dual roles in medulloblastoma, acting as a tumor suppressor by stabilizing p27 and a tumor promoter by stabilizing GLI1, impacting patient outcomes in SHH-driven tumors.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • USP37, a deubiquitylase, regulates protein stability and is implicated in medulloblastoma.
  • SHH signaling pathway activation drives a subset of medulloblastomas.
  • USP37 expression levels correlate with patient outcomes in SHH-medulloblastoma.

Purpose of the Study:

  • To investigate the context-specific roles of USP37 in SHH-driven medulloblastoma.
  • To elucidate the molecular mechanisms underlying USP37's function in medulloblastoma.
  • To identify novel USP37 targets and their impact on tumor progression.

Main Methods:

  • Genetic and biochemical analyses
  • Protein stability assays
  • Western blotting
  • Immunoprecipitation

Main Results:

  • USP37 downregulation is associated with poor outcomes via reduced p27 stabilization, impairing differentiation.
  • USP37 upregulation is linked to poor outcomes via GLI1 stabilization, promoting proliferation.
  • USP37 also targets Raptor, affecting mTORC1 activity and translation initiation.

Conclusions:

  • USP37 exhibits context-dependent tumor suppressive and oncogenic functions in medulloblastoma.
  • USP37's dual role highlights its complex involvement in SHH-driven medulloblastoma.
  • Targeting USP37 may offer therapeutic strategies with careful consideration of its opposing roles.