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UBE2S exerts oncogenic activities in urinary bladder cancer by ubiquitinating TSC1
- Source :
- Biochemical and Biophysical Research Communications. 578:7-14
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Ubiquitin-conjugating enzyme E2S (UBE2S), an important E2 enzyme in the process of ubiquitination, has exhibited oncogenic activities in various malignant tumors. However, it remains unknown whether UBE2S plays a role in urinary bladder cancer (UBC) development. In the current study, our data confirmed UBE2S upregulation in UBC. In vitro and in vivo experiments demonstrated that UBE2S knockdown resulted in attenuated proliferation and enhanced apoptosis, which was inverse to the phenotypes with UBE2S overexpression. Gain and loss of function assays confirmed that UBE2S exerts oncogenic activities in UBC by mediating the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, we discovered that this UBE2S-modulated carcinogenic mechanism was in the consequence of directly targeting tuberous sclerosis 1 (TSC1), which is the upstream inhibitor of mTOR signaling for ubiquitous degradation. Taken together, this study demonstrated that UBE2S is a carcinogen in UBC and promotes UBC progression by ubiquitously degrading TSC1. This consequently mediates the activation of the mTOR pathway, suggesting a potential therapeutic regimen for UBC by targeting the newly identified UBE2S/TSC1/mTOR axis.
- Subjects :
- Biophysics
Mice, Nude
mTORC1
Biology
Biochemistry
Tuberous Sclerosis Complex 1 Protein
Cell Line
Mice
Ubiquitin
Downregulation and upregulation
Cell Line, Tumor
Databases, Genetic
medicine
Animals
Humans
Molecular Biology
Carcinogen
PI3K/AKT/mTOR pathway
Mice, Inbred BALB C
Gene knockdown
TOR Serine-Threonine Kinases
fungi
Ubiquitination
Computational Biology
Cell Biology
Survival Rate
medicine.anatomical_structure
Urinary Bladder Neoplasms
Apoptosis
Ubiquitin-Conjugating Enzymes
biology.protein
Cancer research
Heterografts
TSC1
Signal Transduction
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 578
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....7f53ecec7039efd33a0565d2f2d05d5e