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How a losing a skin protein can lead to cancer

Dystrophic epodermolysis bullosa, or DEB, is a rare, inherited skin fragility disorder characterized by severe skin blistering. Patients’ blisters often heal abnormally, with significant scarring, which can reduce dexterity and range of motion over time. The disorder also comes with a high risk of aggressive skin cancer developing before age 35. DEB is caused by loss-of-function mutations in the gene that codes for collagen VII. Collagen proteins are important structural components of the extracellular matrix. How the loss of collagen VII in epithelial cells contributes to such disease pathology remains ill-understood. In a study published in Molecular & Cellular Proteomics, researchers at the University of Freiburg, led by Jorn Dengjel, performed a global transcriptome and proteome profiling comparing skin cells isolated from patients with DEB to normal human skin cells. The researchers found that loss of collagen VII affected the composition of the cellular microenvironment by reducing the abundance of collagen binding proteins. Loss of collagen VII also led to global changes in how the cell handled mRNA and protein turnover, with increased autophagy and proteolysis in the patient-derived cells compared to controls. The researchers showed that inflammatory and

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