Regulation of PCTAIRE1 protein stability by AKT1, LKB1 and BRCA1

Gillani, Syed Qaaifah; Nisa, Misbah Un; Sarwar, Zarka; Reshi, Irfana; Bhat, Sameer Ahmed; Nabi, Nusrat; Andrabi, Shaida

doi:10.1016/j.cellsig.2021.110032

Cited by 7 publications

(6 citation statements)

References 39 publications

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“…CDK16 encodes a protein kinase involved in neurite outgrowth, vesicle trafficking and cell proliferation. 40 A deletion of two nucleotides leading to a frameshift (NM_006201.5: c.976_977del, p.(Trp326Valfs*5)) segregating in four males with ID, ASD, absence seizures and mild spasticity was reported in this gene by Hu et al 18 Using exome sequencing, we identified a nonsense variant (c.961G>T, p.(Glu321*)) in an adult patient with ID and spasticity. A missense variant (c.1039G>T, p.(Gly347Cys)) affecting a highly conserved amino acid of the kinase domain (CADD PHRED score: 32) was identified by genome sequencing in a male patient with ID, ASD and epilepsy, whose family history was compatible with X-linked inheritance (Fig.…”

Section: Resultsmentioning

confidence: 73%

Systematic analysis and prediction of genes associated with disorders on chromosome X

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et al. 2022

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Disease gene discovery on chromosome (chr) X is challenging owing to its unique modes of inheritance. We undertook a systematic analysis of human chrX genes. We observe a higher proportion of disorder-associated genes and an enrichment of genes involved in cognition, language, and seizures on chrX compared to autosomes. We analyze gene constraints, exon and promoter conservation, expression and paralogues, and report 127 genes sharing one or more attributes with known chrX disorder genes. Using a neural network trained to distin-guish disease-associated from dispensable genes, we classify 235 genes, including 121 of the 127, as having high probability of being disease-associated. We provide evidence of an excess of variants in predicted genes in existing databases. Finally, we report damaging variants in CDK16 and TRPC5 in patients with intellectual disability or autism spectrum disorders. This study predicts large-scale gene-disease associations that could be used for prioritization of X-linked pathogenic variants.

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Section: Resultsmentioning

confidence: 73%

Systematic analysis and prediction of genes associated with disorders on chromosome X

Leitão

Schröder

Parenti

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…CDK16 encodes a protein kinase involved in neurite outgrowth, vesicle trafficking, and cell proliferation 49 . A deletion of two nucleotides leading to a frameshift (NM_006201.5: c.976_977del, p.(Trp326Valfs*5)) segregating in four males with ID, ASD, absence seizures, and mild spasticity was reported in this gene by Hu et al 18 Using exome sequencing, we identified a nonsense variant (c.961 G > T, p.(Glu321*)) in a 42-year-old patient with ID and spasticity.…”

Section: Resultsmentioning

confidence: 99%

Systematic analysis and prediction of genes associated with monogenic disorders on human chromosome X

et al. 2022

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Disease gene discovery on chromosome (chr) X is challenging owing to its unique modes of inheritance. We undertook a systematic analysis of human chrX genes. We observe a higher proportion of disorder-associated genes and an enrichment of genes involved in cognition, language, and seizures on chrX compared to autosomes. We analyze gene constraints, exon and promoter conservation, expression, and paralogues, and report 127 genes sharing one or more attributes with known chrX disorder genes. Using machine learning classifiers trained to distinguish disease-associated from dispensable genes, we classify 247 genes, including 115 of the 127, as having high probability of being disease-associated. We provide evidence of an excess of variants in predicted genes in existing databases. Finally, we report damaging variants in CDK16 and TRPC5 in patients with intellectual disability or autism spectrum disorders. This study predicts large-scale gene-disease associations that could be used for prioritization of X-linked pathogenic variants.

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“…[26,27] AKT is a serine/threonine protein kinase, and AKT1, a heterodimer of AKT, mediates many PI3K-regulated downstream pathways. [28] Some studies have found [29,30] that AKT phosphorylation can also be involved in blood vessel formation through the PKB/AKT pathway. The levels of PI3K and AKT in the chorionic villus cells of spontaneously aborted patients are lower than those of artificially aborted patients, suggesting that the PI3K/AKT pathway can promote the growth of trophoblast cells and regulate the function of chorionic trophoblast cells, suggesting that the PI3K/ AKT pathway has direct and indirect effects on embryonic development and pregnancy maintenance.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacological analysis and molecular docking of Huangqin-Baizhu herb pair in the treatment of threatened abortion

et al. 2022

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Background: The incidence of threatened abortion (TA) is increasing due to poor diet and living habits, which brings great pressure to pregnant women and their families. Huangqin-Baizhu herb pair recorded in ancient books of traditional Chinese medicine has been widely used in the treatment of TA with remarkable effect. In this study, we will use the network pharmacology method to predict the target and mechanism of Huangqin-Baizhu herb pair.Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database was used to screen the active components of Huangqin-Baizhu herb pair. Pubchem and Swiss Target Prediction databases were used to predict the action targets. Genecards, OMIM, and Drugbank databases were used to predict the related targets of TA. The intersection of drug target and disease target was selected and the intersection genes were uploaded to STRING database to construct protein-protein interaction network and conduct module analysis. Metascape database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which was imported into Cytoscape software to construct component-pathway-gene network and finally verified by molecular docking. Ethical approval and informed consent of patients are not required because the data used in this study is publicly available and does not involve individual patient data or privacy. Results:The main active components of the herb pair are baicalein, flavanone, and norwogonin, etc. The main targets are AKT1, VEGFA, STAT3, MAPK1, SRC, etc. Cluster module analysis shows that the targets are related to cell metabolism, immune regulation and hormone level regulation. There were 2073, 3169, and 161 KEGG pathways involved in the biological processes, cell components, and molecular functions of Gene Ontology analysis, respectively. The main KEGG pathways involved in the intervention were HIF1 signaling pathway, PI3K-Akt signaling pathway, and Rap1 signaling pathway. Molecular docking showed that the main active components of the herb pair were well combined with the key targets.Conclusions: In this study, 42 active components, 152 potential targets and 11 key targets of Huangqin-Baizhu herb pair for the treatment of TA were revealed, participating in multiple signaling pathways such as PI3K-Akt, providing a theoretical basis for further experimental research.

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Regulation of PCTAIRE1 protein stability by AKT1, LKB1 and BRCA1

Cited by 7 publications

References 39 publications

Systematic analysis and prediction of genes associated with disorders on chromosome X

Systematic analysis and prediction of genes associated with disorders on chromosome X

Systematic analysis and prediction of genes associated with monogenic disorders on human chromosome X

Network pharmacological analysis and molecular docking of Huangqin-Baizhu herb pair in the treatment of threatened abortion

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