protein kinases
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2022 ◽  
Author(s):  
Tingzhen Wang ◽  
Mingjia Liu ◽  
Yufeng Tian ◽  
Yingyan Han ◽  
Chaojie Liu ◽  
...  

Agronomy ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 125
Author(s):  
Hossein Ahmadi ◽  
Alireza Abbasi ◽  
Alireza Taleei ◽  
Valiollah Mohammadi ◽  
José J. Pueyo

Canola is an important temperate oil crop that can be severely affected by drought. Understanding the physiological and molecular mechanisms involved in canola tolerance to water deficit is essential to obtain drought-tolerant productive cultivars. To investigate the role of antioxidant response and the possible involvement of calcium-dependent protein kinases (CDPKs) in canola tolerance to drought, we analyzed four genotypes with different sensitivity to water stress. Leaf relative water content, canopy temperature, PSII efficiency, electrolyte leakage index and lipid peroxidation were used as indicators to classify the cultivars as drought-tolerant or drought-sensitive. Antioxidant enzymes superoxide dismutase, guaiacol peroxidase and catalase displayed significantly higher activities in drought-tolerant than in drought-sensitive cultivars subjected to water deficit, suggesting that the efficiency of the antioxidant response is essential in canola drought tolerance. The increased expression of genes BnaCDPK6 and BnaCDPK14 under drought conditions, their differential expression in drought-tolerant and drought-sensitive genotypes, and the presence of multiple cis-acting stress-related elements in their promoter regions suggest that CDPKs are part of the signaling pathways that regulate drought response in canola. We propose the BnaCDPK genes and their regulator elements as potential molecular targets to obtain drought-tolerant productive canola cultivars through breeding or genetic transformation.


2022 ◽  
Author(s):  
Safa Daoud ◽  
Mutasem Taha

Abstract Activity cliffs (ACs) are analogous compounds of significant affinity discrepancies against certain biotarget. We propose that the ACs phenomenon is protein-related and that the propensity of certain target to have ACs can be predicted by some intrinsic protein properties. We pursued this assumption by collecting the crystallographic structures of 84 protein kinases, each of which has numerous reported inhibitors (hundreds). Following data augmentation using synthetic minority oversampling technique (SMOTE), we attempted to correlate the presence/absence of ACs within the ligand pools of collected protein kinases with their corresponding protein properties using genetic algorithm (GA) coupled with variety of machine learners (MLs). Very good GA-ML models were achieved with accuracies of around 75% against external testing set. The models were further validated by Y-scrambling. Shapely additive explanations highlighted the significance of protein rotatable bonds, hydrophobic and acidic residues in relation to the presence of ACs. These results support the hypothesis that ACs are protein-related.


Author(s):  
Fuwen Yao ◽  
Yongqiang Zhan ◽  
Changzheng Li ◽  
Ying Lu ◽  
Jiao Chen ◽  
...  

Abnormal activation of protein kinases and phosphatases is implicated in various tumorigenesis, including hepatocellular carcinoma (HCC). Advanced HCC patients are treated with systemic therapy, including tyrosine kinase inhibitors, which extend overall survival. Investigation of the underlying mechanism of protein kinase signaling will help to improve the efficacy of HCC therapy. Combining single-cell RNA sequencing data and TCGA RNA-seq data, we profiled the protein kinases, phosphatases, and other phosphorylation-related genes (PRGs) of HCC patients in this study. We found nine protein kinases and PRGs with high expression levels that were mainly detected in HCC cancer stem cells, including POLR2G, PPP2R1A, POLR2L, PRC1, ITBG1BP1, MARCKSL1, EZH2, DTYMK, and AURKA. Survival analysis with the TCGA dataset showed that these genes were associated with poor prognosis of HCC patients. Further correlation analysis showed that these genes were involved in cell cycle-related pathways that may contribute to the development of HCC. Among them, AURKA and EZH2 were identified as two hub genes by Ingenuity Pathway Analysis. Treatment with an AURKA inhibitor (alisertib) and an EZH2 inhibitor (gambogenic) inhibited HCC cell proliferation, migration, and invasion. We also found that both AURKA and EZH2 were highly expressed in TP53-mutant HCC samples. Our comprehensive analysis of PRGs contributes to illustrating the mechanisms underlying HCC progression and identifying potential therapeutic targets for future clinical trials.


2022 ◽  
pp. 112814
Author(s):  
Jeong-Won Kim ◽  
Jin-Hwa Kim ◽  
Chang-Yeop Kim ◽  
Ji-Soo Jeong ◽  
Je-Oh Lim ◽  
...  

RSC Advances ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 561-577
Author(s):  
Ismail M. M. Othman ◽  
Zahra M. Alamshany ◽  
Nada Y. Tashkandi ◽  
Mohamed A. M. Gad-Elkareem ◽  
Somaia S. Abd El-Karim ◽  
...  

Deregulation of various protein kinases is considered as one of the important factors resulting in cancer development and metastasis, thus multi-targeting the kinase family is one of the most important strategies in current cancer therapy.


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