quantitative proteomics reveals cellular targets of celastrol定量蛋白质组学揭示细胞celastrol的目标.pdfVIP

Quantitative Proteomics Reveals Cellular Targets of Celastrol 1,2 ¤ 1 1,3 4 1 1 Jakob Hansen * , Johan Palmfeldt , Søren Vang , Thomas J. Corydon , Niels Gregersen , Peter Bross 1 Research Unit for Molecular Medicine, Aarhus University Hospital, Skejby, Aarhus, Denmark, 2 Department of Forensic Medicine, Aarhus University, Aarhus, Denmark, 3 Department of Molecular Medicine, Aarhus University Hospital, Skejby, Aarhus, Denmark, 4 Department of Human Genetics, Aarhus University, Aarhus, Denmark Abstract Celastrol, a natural substance isolated from plant extracts used in traditional Chinese medicine, has been extensively investigated as a possible drug for treatment of cancer, autoimmune diseases, and protein misfolding disorders. Although studies focusing on celastrol’s effects in specific cellular pathways have revealed a considerable number of targets in a diverse array of in vitro models there is an essential need for investigations that can provide a global view of its effects. To assess cellular effects of celastrol and to identify target proteins as biomarkers for monitoring treatment regimes, we performed large-scale quantitative proteomics in cultured human lymphoblastoid cells, a cell type that can be readily prepared from human blood samples. Celastrol substantially modified the proteome composition and 158 of the close to 1800 proteins with robust quantitation showed at least a 1.5 fold change in protein levels. Up-regulated proteins play key roles in cytoprotection with a prominent group involved in quality control and processing of proteins traversing the endoplasmic reticulum. Increased levels of proteins essential for the c