image: Researchers comparing protein expression in skin tissue from patients with dystrophic epodermolysis bullosa (DEB), which causes blistering and scarring, to tissue from healthy controls have shown increased inflammation and proteolysis in patient tissue. The proteomic results may uncover future treatment strategies for the rare genetic disorder, caused by mutation to collagen VII. view more
Credit: Kerstin Thriene and Jörn Dengjel, Department of Dermatology, Medical Center, University of Freiburg, Germany
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 proteolytic processes were perturbed in DEB cells both in vitro and in vivo. The study provides a global yet detailed picture of dysregulated molecular consequences of collagen VII deficiency, and may present a path toward new treatment strategies for the uncurable disorder.
doi:10.1074/mcp.RA117.000437
http://www.mcponline.org/content/early/2018/01/11/mcp.RA117.000437.abstract
Characterizing protein changes in T cell activation using novel proteomics
Post-translational modifications of proteins are important for activation of T cells during an immune response. One of these modifications, called O-GlcNAc, involves the addition of a sugar molecule onto proteins. Addition of O-GlcNAc is known to be involved in the activation of T cells; however its function on most glycoproteins remains unknown due to difficulty in finding and mapping O-GlcNAc sites. In a study published in Molecular & Cellular Proteomics, investigators at Harvard and Stanford universities led by Christina Woo employed a method called IsoTaG to catalogue and quantify the O-GlcNAc sites in resting and activated human T cells. IsoTaG works by metabolically labeling O-GlcNAc residues and tagging them via click chemistry with a probe to enable enrichment and subsequent identification using mass spectrometry. The investigators identified 2,219 O-GlcNAcylated peptides from 1,045 glycoproteins, the most comprehensive characterization of O-GlcNAc modification sites ever. Using gel shift assays, they further confirmed the quantitative findings of a number of proteins that showed significant changes during T-cell activation. The results provide a valuable resource for future studies aimed at a mechanistic understanding of the function of O-GlcNAc on specific proteins during T cell activation.
doi:10.1074/mcp.RA117.000261
http://www.mcponline.org/content/early/2018/01/19/mcp.RA117.000261.abstract
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Molecular & Cellular Proteomics (MCP) showcases research into proteomes, large-scale sets of proteins from different organisms or biological contexts. The journal publishes work that describes the structural and functional properties of proteins and their expression, particularly with respect to developmental time courses. Emphasis is placed on determining how the presence or absence of proteins affect biological responses, and how the interaction of proteins with their cellular partners influences their functions. For more information about MCP, visit http://www.mcponline.org.
About the American Society for Biochemistry and Molecular Biology
The ASBMB is a nonprofit scientific and educational organization with more than 11,000 members worldwide. Most members teach and conduct research at colleges and universities. Others conduct research in government laboratories, at nonprofit research institutions and in industry. The Society's student members attend undergraduate or graduate institutions. For more information about ASBMB, visit http://www.asbmb.org.
Journal
Molecular & Cellular Proteomics