1 research outputs found
Proteomic Profile Identifies Dysregulated Pathways in Cornelia de Lange Syndrome Cells with Distinct Mutations in <i>SMC1A</i> and <i>SMC3</i> 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, <i>SMC1A</i> and <i>SMC3</i>. 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 <i>c-MYC</i> 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