Proteomic Profile Identifies Dysregulated Pathways in Cornelia de Lange Syndrome Cells with Distinct Mutations in SMC1A and SMC3 Genes
Copyright policy )Proteomic Profile Identifies Dysregulated Pathways in Cornelia de Lange Syndrome Cells with Distinct Mutations in SMC1A and SMC3 Genes
Mutations in cohesin genes have been identified in Cornelia de Lange syndrome (CdLS), but its etiopathogenetic mechanisms are still poorly understood. To define biochemical pathways that are affected in CdLS, we analyzed the proteomic profile of CdLS cell lines carrying mutations in the core cohesin genes, SMC1A and SMC3. Dysregulated protein expression was found in CdLS probands compared to controls. The proteomics analysis was able to discriminate between probands harboring mutations in the different domains of the SMC proteins. In particular, proteins involved in the response to oxidative stress were specifically down-regulated in hinge mutated probands. In addition, the finding that CdLS cell lines show an increase in global oxidative stress argues that it could contribute to some CdLS phenotypic features such as premature physiological aging and genome instability. Finally, the c-MYC gene represents a convergent hub lying at the center of dysregulated pathways, and is down-regulated in CdLS. This study allowed us to highlight, for the first time, specific biochemical pathways that are affected in CdLS, providing plausible causal evidence for some of the phenotypic features seen in CdLS.
- National Research Council Italy
- Children's Hospital of Philadelphia United States
- University of Siena Italy
- Institute of Genetic and Biomedical Research Italy
Male, 570, Chromosomal Proteins, Non-Histone, Molecular Sequence Data, Primary Cell Culture, cohesin, dysregulated protein expression, Cell Cycle Proteins, SMC3, proteomic profile, Genomic Instability, Mass Spectrometry, SMC1A, De Lange Syndrome, Humans, Amino Acid Sequence, Nuclear Proteins, Phosphoproteins, Cornelia de Lange syndrome, cohesin, Cornelia de Lange syndrome, SMC1A, SMC3, 2D-DIGE, proteomic profile, dysregulated protein expression, c-Myc, DNA-Binding Proteins, Oxidative Stress, c-Myc, Phenotype, Chondroitin Sulfate Proteoglycans, Gene Expression Regulation, Case-Control Studies, Mutation, 2D-DIGE, Female
Male, 570, Chromosomal Proteins, Non-Histone, Molecular Sequence Data, Primary Cell Culture, cohesin, dysregulated protein expression, Cell Cycle Proteins, SMC3, proteomic profile, Genomic Instability, Mass Spectrometry, SMC1A, De Lange Syndrome, Humans, Amino Acid Sequence, Nuclear Proteins, Phosphoproteins, Cornelia de Lange syndrome, cohesin, Cornelia de Lange syndrome, SMC1A, SMC3, 2D-DIGE, proteomic profile, dysregulated protein expression, c-Myc, DNA-Binding Proteins, Oxidative Stress, c-Myc, Phenotype, Chondroitin Sulfate Proteoglycans, Gene Expression Regulation, Case-Control Studies, Mutation, 2D-DIGE, Female
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).42 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!