Posttranslational Modifications of Smurfs: Emerging Regulation in Cancer

Yang, Longtao; Zhou, Wenwen; Lin, Hui

doi:10.3389/fonc.2020.610663

Cited by 4 publications

(5 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The activity of TGF-β/Smad pathway is known to be regulated by ubiquitination at multiple levels [ 25 ]. As E3 ubiquitin ligases, Smad ubiquitination regulatory factors (Smurfs) play an important role in mediating the ubiquitination and degradation of TGF-β/Smad pathway proteins [ 26 ]. Therefore, we speculated that ARK5 regulates TβRI and Smad4 degradation by modulating the expression of Smurfs.…”

Section: Resultsmentioning

confidence: 99%

“…Our further studies confirmed that TβRI and Smad4 are indeed degraded by ubiquitination. Smurfs belong to the Nedd4 subfamily of HECT-type E3 ubiquitin ligases and are involved in the ubiquitination and degradation of various TGF-β pathway-related proteins [ 26 ]. Therefore, we next tested whether knockdown of ARK5 could affect the expression of Smurfs.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Enhanced Expression of ARK5 in Hepatic Stellate Cell and Hepatocyte Synergistically Promote Liver Fibrosis

You

Gao

et al. 2022

IJMS

View full text Add to dashboard Cite

AMPK-related protein kinase 5 (ARK5) is involved in a broad spectrum of physiological and cell events, and aberrant expression of ARK5 has been observed in a wide variety of solid tumors, including liver cancer. However, the role of ARK5 in liver fibrosis remains largely unexplored. We found that ARK5 expression was elevated in mouse fibrotic livers, and showed a positive correlation with the progression of liver fibrosis. ARK5 was highly expressed not only in activated hepatic stellate cells (HSCs), but also in hepatocytes. In HSCs, ARK5 prevents the degradation of transforming growth factor β type I receptor (TβRI) and mothers against decapentaplegic homolog 4 (Smad4) proteins by inhibiting the expression of Smad ubiquitin regulatory factor 2 (Smurf2), thus maintaining the continuous transduction of the transforming growth factor β (TGF-β) signaling pathway, which is essential for cell activation, proliferation and survival. In hepatocytes, ARK5 induces the occurrence of epithelial-mesenchymal transition (EMT), and also promotes the secretion of inflammatory factors. Inflammatory factors, in turn, further enhance the activation of HSCs and deepen the degree of liver fibrosis. Notably, we demonstrated in a mouse model that targeting ARK5 with the selective inhibitor HTH-01-015 attenuates CCl4-induced liver fibrosis in mice. Taken together, the results indicate that ARK5 is a critical driver of liver fibrosis, and promotes liver fibrosis by synergy between HSCs and hepatocytes.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Enhanced Expression of ARK5 in Hepatic Stellate Cell and Hepatocyte Synergistically Promote Liver Fibrosis

You

Gao

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…In recent years, a growing number of evidence has suggested that PTM was closely related to cell survival, cell cycle, differentiation, and innate and adaptive immunity for multiple cancer ( Wu et al, 2019 ; Chen et al, 2020 ; Yang et al, 2020 ). As one of the most important PTM, ubiquitination has also attracted much attention in OS ( Chen et al, 2014 ; Ying et al, 2016 ; Zhao et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

A ubiquitin-related gene signature for predicting prognosis and constructing molecular subtypes in osteosarcoma

Gong

Wen-ming

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Background: Ubiquitination is medicated by three classes of enzymes and has been proven to involve in multiple cancer biological processes. Moreover, dysregulation of ubiquitination has received a growing body of attention in osteosarcoma (OS) tumorigenesis and treatment. Therefore, our study aimed to identify a ubiquitin-related gene signature for predicting prognosis and immune landscape and constructing OS molecular subtypes.Methods: Therapeutically Applicable Research to Generate Effective Treatments (TARGET) was regarded as the training set through univariate Cox regression, Lasso Cox regression, and multivariate Cox regression. The GSE21257 and GSE39055 served as the validation set to verify the predictive value of the signature. CIBERSORT was performed to show immune infiltration and the immune microenvironment. The NMF algorithm was used to construct OS molecular subtypes.Results: In this study, we developed a ubiquitin-related gene signature including seven genes (UBE2L3, CORO6, DCAF8, DNAI1, FBXL5, UHRF2, and WDR53), and the gene signature had a good performance in predicting prognosis for OS patients (AUC values at 1/3/5 years were 0.957, 0.890, and 0.919). Multivariate Cox regression indicated that the risk score model and prognosis stage were also independent prognostic prediction factors. Moreover, analyses of immune cells and immune-related functions showed a significant difference in different risk score groups and the three clusters. The drug sensitivity suggested that IC50 of proteasome inhibitor (MG-132) showed a notable significance between the risk score groups (p < 0.05). Through the NMF algorithm, we obtained the three clusters, and cluster 3 showed better survival outcomes. The expression of ubiquitin-related genes (CORO6, UBE2L3, FBXL5, DNAI1, and DCAF8) showed an obvious significance in normal and osteosarcoma tissues.Conclusion: We developed a novel ubiquitin-related gene signature which showed better predictive prognostic ability for OS and provided additional information on chemotherapy and immunotherapy. The OS molecular subtypes would also give a useful guide for individualized therapy.

show abstract

“…Research by Yang L et al demonstrates that the functional activity of Smurfs is regulated by an array of PTMs, including phosphorylation, ubiquitination, demethylation, and methylation. These modifications are critical in orchestrating the dynamic processes associated with EMT and subsequent tumor invasion [ 38 ]. This suggests that targeting PTMs to modulate EMT could be a viable strategy to impede tumorigenesis and the development of cancer stem cells.…”

Section: Ptms and Emtmentioning

confidence: 99%

Post-translational modifications: The potential ways for killing cancer stem cells

Han,

Qin,

et al. 2024

Heliyon

View full text Add to dashboard Cite

Posttranslational Modifications of Smurfs: Emerging Regulation in Cancer

Cited by 4 publications

References 110 publications

Enhanced Expression of ARK5 in Hepatic Stellate Cell and Hepatocyte Synergistically Promote Liver Fibrosis

Enhanced Expression of ARK5 in Hepatic Stellate Cell and Hepatocyte Synergistically Promote Liver Fibrosis

A ubiquitin-related gene signature for predicting prognosis and constructing molecular subtypes in osteosarcoma

Post-translational modifications: The potential ways for killing cancer stem cells

Contact Info

Product

Resources

About