Prediction of protein ubiquitination sites via multi-view features based on eXtreme gradient boosting classifier

Liu, Yushuang; Jin, Shuping; Song, Lili; Yu, Han; Yu, Bin

doi:10.1016/j.jmgm.2021.107962

“…Nonetheless, several concerns must be taken into account when developing drugs based on the PTMs of Keap1 to facilitate future clinical applications. Firstly, the activation of downstream antioxidant genes in the Keap1-Nrf2 pathway is primarily mediated by Nrf2, while the regulation of Nrf2 itself is not solely dependent on Keap1 ( Liu et al, 2021b ). Additionally, excessive activation of Nrf2 can lead to physiological abnormalities, underscoring the importance of controlling drug release to minimize adverse reactions.…”

Section: Discussionmentioning

confidence: 99%

Post-translational modifications of Keap1: the state of the art

Song,

Qu,

Mao

et al. 2024

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The Keap1-Nrf2 signaling pathway plays a crucial role in cellular defense against oxidative stress-induced damage. Its activation entails the expression and transcriptional regulation of several proteins involved in detoxification and antioxidation processes within the organism. Keap1, serving as a pivotal transcriptional regulator within this pathway, exerts control over the activity of Nrf2. Various post-translational modifications (PTMs) of Keap1, such as alkylation, glycosylation, glutathiylation, S-sulfhydration, and other modifications, impact the binding affinity between Keap1 and Nrf2. Consequently, this leads to the accumulation of Nrf2 and its translocation to the nucleus, and subsequent activation of downstream antioxidant genes. Given the association between the Keap1-Nrf2 signaling pathway and various diseases such as cancer, neurodegenerative disorders, and diabetes, comprehending the post-translational modification of Keap1 not only deepens our understanding of Nrf2 signaling regulation but also contributes to the identification of novel drug targets and biomarkers. Consequently, this knowledge holds immense importance in the prevention and treatment of diseases induced by oxidative stress.

show abstract

“…Computational tool of prediction is a helpful alternative. This type of tools has gained great popularity with the increasing interest on the identification of ubiquitination sites; thus, many prediction tools have been developed [40][41][42][43][44][45][46] . However, most of these tools yield small-scale protein datasets.…”

Section: Discussionmentioning

confidence: 99%

Lysine 222 in PPAR γ1 functions as the key site of MuRF2-mediated ubiquitination modification

Fan

¹

,

Xu²,

Wang³

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptor gamma (PPAR γ) plays key roles in the development, physiology, reproduction, and homeostasis of organisms. Its expression and activity are regulated by various posttranslational modifications. We previously reported that E3 ubiquitin ligase muscle ring finger protein 2 (MuRF2) inhibits cardiac PPAR γ1 protein level and activity, eventually protects heart from diabetic cardiomyopathy; furthermore, by GST-pulldown assay, we found that MuRF2 modifies PPAR γ1 via poly-ubiquitination and accelerates PPAR γ1 proteasomal degradation. However, the key ubiquitination site on PPAR γ that MuRF2 targets for remains unclear. In the present study, we demonstrate that lysine site 222 is the receptor of MuRF2-mediated PPAR γ1 ubiquitination modification, using prediction of computational models, immunoprecipitation, ubiquitination assays, cycloheximide chasing assay and RT-qPCR. Our findings elucidated the underlying details of MuRF2 prevents heart from diabetic cardiomyopathy through the PPAR γ1 regulatory pathway.

show abstract

“…Support vector machine (SVM) software is a widely used machine learning method for classi cation, regression, and other learning tasks in many areas (46,47). Based on SVM algorithm, Huang et al designed the predictor known as UbiSite (39,40). To construct the predictor, the researchers not only assessed the single features of amino acid composition, amino acid pair composition and evolutionary information, but also incorporated two or more features into a hybrid approach.…”

Section: Discussionmentioning

confidence: 99%

Lysine 222 in PPAR γ1 functions as the key site of MuRF2-mediated ubiquitination modification

Fan

¹

,

Xu

²

,

Wang

³

et al. 2022

Preprint

0

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptor gamma (PPAR γ) plays key roles in the development, physiology, reproduction, and homeostasis of organisms. Its expression and activity are regulated by various posttranslational modifications. We previously reported that E3 ubiquitin ligase muscle ring finger protein 2 (MuRF2) inhibits cardiac PPAR γ1 protein level and activity, eventually protects heart from diabetic cardiomyopathy; furthermore, by GST-pulldown assay, we found that MuRF2 modifies PPAR γ1 via poly-ubiquitination and accelerates PPAR γ1 proteasomal degradation. However, the key ubiquitination site on PPAR γ that MuRF2 targets for remains unclear. In the present study, we demonstrate that lysine site 222 is the receptor of MuRF2-mediated PPAR γ1 ubiquitination modification, using prediction of computational models, immunoprecipitation, ubiquitination assays, cycloheximide chasing assay and RT-qPCR. Our findings elucidated the underlying details of MuRF2 prevents heart from diabetic cardiomyopathy through the PPAR γ1 regulatory pathway.

show abstract

Prediction of protein ubiquitination sites via multi-view features based on eXtreme gradient boosting classifier

Cited by 11 publications

References 92 publications

Post-translational modifications of Keap1: the state of the art

Post-translational modifications of Keap1: the state of the art

Lysine 222 in PPAR γ1 functions as the key site of MuRF2-mediated ubiquitination modification

Lysine 222 in PPAR γ1 functions as the key site of MuRF2-mediated ubiquitination modification

Contact Info

Product

Resources

About