Glioma stem cells (GSCs) contribute to the pathogenesis of glioblastoma, the most malignant form of glioma. The implication and underlying mechanisms of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) on the GSC phenotypes remain unknown. We previously demonstrated that SMURF2 phosphorylation at Thr (SMURF2) activates its E3 ubiquitin ligase activity. Here, we demonstrate that SMURF2 phosphorylation plays an essential role in maintaining GSC stemness and tumorigenicity. SMURF2 silencing augmented the self-renewal potential and tumorigenicity of patient-derived GSCs. The SMURF2 phosphorylation level was low in human glioblastoma pathology specimens. Introduction of the SMURF2 mutant resulted in increased stemness and tumorigenicity of GSCs, recapitulating the SMURF2 silencing. Moreover, the inactivation of SMURF2 phosphorylation increases TGF-β receptor (TGFBR) protein stability. Indeed, TGFBR1 knockdown markedly counteracted the GSC phenotypes by SMURF2 mutant. These findings highlight the importance of SMURF2 phosphorylation in maintaining GSC phenotypes, thereby demonstrating a potential target for GSC-directed therapy.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752672 | PMC |
| http://dx.doi.org/10.1038/s42003-021-02950-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
CHK1 attenuates cardiac dysfunction via suppressing SIRT1-ubiquitination.
Metabolism
January 2025
Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address:
Background: Mitochondrial dysfunction is linked to myocardial ischemia-reperfusion (I/R) injury. Checkpoint kinase 1 (CHK1) could facilitate cardiomyocyte proliferation, however, its role on mitochondrial function in I/R injury remains unknown.
Methods: To investigate the role of CHK1 on mitochondrial function following I/R injury, cardiomyocyte-specific knockout/overexpression mouse models were generated.
A regulatory loop involving the cytochrome P450-soluble epoxide hydrolase axis and TGF-β signaling.
iScience
October 2024
Goethe University, Institute for Vascular Signalling, Centre for Molecular Medicine, Frankfurt am Main, Germany.
Article Synopsis
- Fatty acid metabolites from cytochrome P450 enzymes and soluble epoxide hydrolase (sEH) play crucial roles in regulating inflammation, particularly through macrophage polarization.
- * The study reveals that transforming growth factor β (TGF-β) triggers macrophages to adopt a pro-resolving phenotype by activating Alk5 and Smad2, which boosts sEH expression and activity.
- * Macrophages lacking sEH showed poorer repolarization and phagocytosis, with findings indicating an autocrine feedback loop between sEH, its metabolite 11,12-EET, and TGF-β1 that influences macrophage behavior.*
The regulatory roles of Smad2/3 protein and gene expression in granulosa cells of germinal vesicle and metaphase II oocytes in polycystic ovarian syndrome: A case-control study.
Int J Reprod Biomed
June 2024
Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Background: The impaired functions of granulosa cells (GCs) in the delayed development and immaturity of oocytes have been reported in polycystic ovary syndrome (PCOs). Even with ovarian stimulation, a large number of oocytes in these patients are still in the stage germinal vesicle (GV).
Objective: The levels of Smad2/3, phosphorylated Smad2/3 (P-Smad2/3), the expression of , , and genes in the GCs surrounding metaphase II (MII) or GV oocytes in PCOs women were investigated.
FOXO1 regulates RUNX2 ubiquitination through SMURF2 in calcific aortic valve disease.
Redox Biol
July 2024
Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China. Electronic address:
The prevalence of calcific aortic valve disease (CAVD) remains substantial while there is currently no medical therapy available. Forkhead box O1 (FOXO1) is known to be involved in the pathogenesis of cardiovascular diseases, including vascular calcification and atherosclerosis; however, its specific role in calcific aortic valve disease remains to be elucidated. In this study, we identified FOXO1 significantly down-regulated in the aortic valve interstitial cells (VICs) of calcified aortic valves by investigating clinical specimens and GEO database analysis.
View Article and Find Full Text PDFThe miR-15b-Smurf2-HSP27 axis promotes pulmonary fibrosis.
J Biomed Sci
January 2023
Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52, Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Republic of Korea.
Background: Heat shock protein 27 (HSP27) is overexpressed during pulmonary fibrosis (PF) and exacerbates PF; however, the upregulation of HSP27 during PF and the therapeutic strategy of HSP27 inhibition is not well elucidated.
Methods: We have developed a mouse model simulating clinical stereotactic body radiotherapy (SBRT) with focal irradiation and validated the induction of RIPF. HSP25 (murine form of HSP27) transgenic (TG) and LLC1-derived orthotropic lung tumor models were also used.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!