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Genome Research
Article
License: CC BY NC
Data sources: UnpayWall
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PubMed Central
Other literature type . 2013
License: CC BY NC
Data sources: PubMed Central
Genome Research
Article . 2013 . Peer-reviewed
Data sources: Crossref
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Proteome-wide discovery of mislocated proteins in cancer

Authors: Lee, KiYoung; Byun, Kyunghee; Hong, Wonpyo; Chuang, Han-Yu; Pack, Chan-Gi; Bayarsaikhan, Enkhjargal; Paek, Sun Ha; +4 Authors

Proteome-wide discovery of mislocated proteins in cancer

Abstract

Several studies have sought systematically to identify protein subcellular locations, but an even larger task is to map which of these proteins conditionally relocates in disease (the mislocalizome). Here, we report an integrative computational framework for mapping conditional location and mislocation of proteins on a proteome-wide scale, called a conditional location predictor (CoLP). Using CoLP, we mapped the locations of over 10,000 proteins in normal human brain and in glioma. The prediction showed 0.9 accuracy using 100 location tests of 20 randomly selected proteins. Of the 10,000 proteins, over 150 have a strong likelihood of mislocation under glioma, which is striking considering that few mislocation events have been identified in this disease previously. Using immunofluorescence and Western blotting in both primary cells and tissues, we successfully experimentally confirmed 15 mislocations. The most common type of mislocation occurs between the endoplasmic reticulum and the nucleus; for example, for RNF138, TLX3, and NFRKB. In particular, we found that the gene for the mislocating protein GFRA4 had a nonsynonymous point mutation in exon 2. Moreover, redirection of GFRA4 to its normal location, the plasma membrane, led to marked reductions in phospho-STAT3 and proliferation of glioma cells. This framework has the potential to track changes in protein location in many human diseases.

Keywords

Homeodomain Proteins, STAT3 Transcription Factor, Glial Cell Line-Derived Neurotrophic Factor Receptors, Proteome, Brain Neoplasms, Ubiquitin-Protein Ligases, Proto-Oncogene Proteins c-ret, Method, Brain, Kinesins, Molecular Sequence Annotation, Nerve Tissue Proteins, Glioma, Zebrafish Proteins, Protein Transport, Gene Ontology, Homeobox Protein Nkx-2.2, Disease Progression, Humans, Cell Proliferation, Transcription Factors

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
53
Top 10%
Top 10%
Top 10%
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