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Updated: May 23, 2025

Growth-based Determination and Biochemical Confirmation of Genetic Requirements for Protein Degradation in Saccharomyces cerevisiae
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Growth-based Determination and Biochemical Confirmation of Genetic Requirements for Protein Degradation in Saccharomyces cerevisiae

Published on: February 16, 2015

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SOD2 is a regulator of proteasomal degradation promoting an adaptive cellular starvation response

Nurul Khalida Ibrahim1, Sabine Schreek1, Buesra Cinar1

  • 1Department of Pediatric Hematology and Oncology, Hannover Medical School, 30625 Hannover, Germany.

Cell Reports
|March 25, 2025
PubMed

Insights

Superoxide dismutase 2 (SOD2) regulates protein degradation to help cancer cells survive amino acid starvation. Inhibiting this function sensitizes cancer to nutrient deprivation, revealing a new therapeutic target.

Area of Science:

  • Cellular Biology
  • Cancer Metabolism
  • Biochemistry

Background:

  • Cellular homeostasis relies on adapting to amino acid availability.
  • Cancer cells exhibit unique mechanisms to survive nutrient stress.
  • The role of superoxide dismutase 2 (SOD2) in cancer metabolism is not fully understood.

Purpose of the Study:

  • To investigate the function of SOD2 beyond its dismutase activity in cancer.
  • To identify mechanisms cancer cells use to maintain fitness during amino acid shortage.
  • To explore SOD2 as a potential therapeutic target in cancer.

Main Methods:

  • Genome-wide CRISPR-Cas9 screening.
  • Assays for proteasomal protein degradation.
  • Cell survival studies under metabolic stress.
  • Experiments using cancer cell lines and patient-derived xenografts.

Main Results:

  • SOD2 has a dismutase-independent function regulating global proteasomal protein degradation.
  • SOD2 promotes cancer cell survival under amino acid starvation via E3 ubiquitin ligases UBR1 and UBR2.
  • Inhibition of SOD2-mediated degradation sensitizes various cancers to amino acid depletion.

Conclusions:

  • SOD2 is a key regulator of proteasomal protein breakdown during starvation.
  • This mechanism provides an independent amino acid source, exploited by cancer cells.
  • Targeting SOD2-dependent protein degradation offers a promising strategy against cancer.
Keywords:
CP: CancerCP: Molecular biologySOD2UBR1UBR2amino acid starvationcancerdrug resistanceleukemiaprotein degradation

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