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Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
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UBE2S exerts oncogenic activities in urinary bladder cancer by ubiquitinating TSC1

Hao Tang1, Tong Fang1, Meng Ji2

  • 1Department of College of Clinical Medicine of Weifang Medical University, Weifang, China.

Biochemical and Biophysical Research Communications
|September 14, 2021
PubMed

Insights

Ubiquitin-conjugating enzyme E2S (UBE2S) promotes urinary bladder cancer (UBC) by degrading TSC1, activating the mTOR pathway. Targeting UBE2S offers a potential therapeutic strategy for UBC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Ubiquitin-conjugating enzyme E2S (UBE2S) is implicated in various cancers.
  • The role of UBE2S in urinary bladder cancer (UBC) is not yet understood.

Purpose of the Study:

  • To investigate the role and mechanism of UBE2S in UBC development.
  • To explore UBE2S as a potential therapeutic target for UBC.

Main Methods:

  • Quantitative real-time PCR to confirm UBE2S upregulation in UBC tissues.
  • In vitro and in vivo experiments involving UBE2S knockdown and overexpression.
  • Gain and loss of function assays to assess UBE2S's impact on cell proliferation and apoptosis.
  • Western blotting to analyze the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway and tuberous sclerosis 1 (TSC1) degradation.

Main Results:

  • UBE2S was found to be upregulated in UBC.
  • UBE2S knockdown inhibited UBC cell proliferation and promoted apoptosis, while overexpression had the opposite effect.
  • UBE2S activates the mTORC1 pathway by directly targeting TSC1 for degradation.
  • UBE2S functions as an oncogene in UBC by promoting tumor progression through the UBE2S/TSC1/mTOR axis.

Conclusions:

  • UBE2S is a significant driver of UBC progression.
  • The UBE2S/TSC1/mTOR signaling pathway represents a novel therapeutic target for UBC treatment.
Keywords:
Bladder cancerTSC1UBE2SUbiquitination

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