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Translational medicine concerns the elucidation of molecular mechanisms of disease processes, the mapping ofpathological cellular network and identification of potential biochemical targets to develop new drug ("from thebench to bedside and bedside to bench"). Proteomic based approaches are powerful tools with great promise in disease diagnosis and mechanistic profiling oftherapeutic interventions. This special issue will focus on recent advances in the application of proteomic, includingseveral aspects of clinical proteomic, biomarker discovery, systems biology using computational models,elucidation of cellular networks, and finally important functional and posttranslational modifications regulating cellsignaling. Cellular signaling is no longer considered as a linear pathway from the cells exterior to the nucleus. Stimulatory andinhibitory interconnected pathways are induced in parallel and often involve synergistic as well as antagonisticinterplay between specific signaling pathway components. Thus, mapping of entire cellular signaling pathwaysseems to be required to elucidate how proteins are regulated in both healthy and pathological signaling. To make sense of such complex network we must couple quantitative experimental data with computationalmodeling and bioinformatics. Dr. Kleppe et al. cover the use of proteomic and computational methods in systemsmodeling of cellular signaling. Biomarkers discovery are the basis for early diagnosis and prognosis of disease. Dr. Berven and co-workers give acomprehensive overview of proteomic based biomarker discovery with emphasis on cerebrospinal fluid andmultiple sclerosis. The next four papers present diverse clinical proteomic-based methods for diagnosis and therapeutic interventionsof acute myeloid leukemia. Dr. Sjoholt et al. present proteomic strategies for individualizing therapy of myeloid leukemia. Diagnostic, prognostic and therapeutic exploitation of telomeres and telomerase are covered by Dr. L. Deville andcolleagues. Some of the anti-telomerase strategies show promising effects for the treatment of leukemia. The tyrosine kinase inhibitor Imatinib mesylate is successfully used for targeting the fusion protein Bcr/Abl. Dr.Oveland et al. describe proteomic approaches to elucidate oncogenic tyrosine kinase signaling in myeloidmalignancies. An overview of proteomic of p53 in diagnostic and therapy of acute myeloid leukemia is presented by Dr. Ånesenand co-workers. The numerous posttranslational modifications of the p53 protein are given special attention. Posttranslational phosphorylation has a crucial role in regulation of cellular signaling. Dr. Solstad and Dr. Fladmarkmake available a practical approach for identification of low abundance phosphoproteins by using algal toxins asguidance to identify phosphoproteins with key roles in apoptotic cell. Proteomic studies on the 14-3-3 interactome are presented by Dr. Kjærland et al., and they pose the question "Doesisoform diversity explain functional differences in the 14-3-3 protein family?".