2016
DOI: 10.7554/elife.16950
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Global, quantitative and dynamic mapping of protein subcellular localization

Abstract: Subcellular localization critically influences protein function, and cells control protein localization to regulate biological processes. We have developed and applied Dynamic Organellar Maps, a proteomic method that allows global mapping of protein translocation events. We initially used maps statically to generate a database with localization and absolute copy number information for over 8700 proteins from HeLa cells, approaching comprehensive coverage. All major organelles were resolved, with exceptional pr… Show more

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Cited by 495 publications
(850 citation statements)
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“…22 While this concept is usually brought up in the context of in vivo efficacy, it has been reported to impact cellular efficacy as well. 23 Given the high concentration of intracellular LDH (estimated to be in the range of 2–17 μM), 11,24 we reasoned that longer residence times might be necessary to achieve significant, sustained decreases in cellular LDH function. As noted above, this approach could also be beneficial in vivo , since drug concentration in systemic circulation decreases with time and LDH is an abundant, ubiquitously expressed protein.…”
Section: Resultsmentioning
confidence: 99%
“…22 While this concept is usually brought up in the context of in vivo efficacy, it has been reported to impact cellular efficacy as well. 23 Given the high concentration of intracellular LDH (estimated to be in the range of 2–17 μM), 11,24 we reasoned that longer residence times might be necessary to achieve significant, sustained decreases in cellular LDH function. As noted above, this approach could also be beneficial in vivo , since drug concentration in systemic circulation decreases with time and LDH is an abundant, ubiquitously expressed protein.…”
Section: Resultsmentioning
confidence: 99%
“…This is critical for selecting appropriate spatial references and for determining their relative contribution to the quantitative proteomic analysis at each time point. Information about subcellular location is already available for many proteins, including other signaling receptors, and there has been considerable recent progress in development of methods to define the subcellular location of target proteins more broadly (Itzhak et al, 2016; Lundberg and Uhlén, 2010; Marx, 2015; Rhee et al, 2013). In addition, we note that the present APEX methodology inherently returns information regarding subcellular location (Figures 3B and S2A).…”
Section: Discussionmentioning
confidence: 99%
“…To generate an unbiased annotation of the localization of the protein products of the genes included in the GI map (e.g. Figure 5C), we leveraged two recently published datasets: the mass-spectrometry-based Map of the Cell (Itzhak et al, 2016) and the immunofluorescence-based Cell Atlas (Thul et al, 2017). Together, these annotations contained localization predictions for the large majority of genes in the GI map and could be used to refine localization in cases where one dataset gave ambiguous calls.…”
Section: Star Methodsmentioning
confidence: 99%