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Secretome-Based Screening in Target Discovery

Secreted proteins and their cognate plasma membrane receptors regulate human physiology by transducing signals from the extracellular environment into cells resulting in different cellular phenotypes. Systematic use of secretome proteins in assays enables discovery of novel biology and signaling pat...

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Autores principales: Ding, Mei, Tegel, Hanna, Sivertsson, Åsa, Hober, Sophia, Snijder, Arjan, Ormö, Mats, Strömstedt, Per-Erik, Davies, Rick, Holmberg Schiavone, Lovisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309359/
https://www.ncbi.nlm.nih.gov/pubmed/32425085
http://dx.doi.org/10.1177/2472555220917113
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author Ding, Mei
Tegel, Hanna
Sivertsson, Åsa
Hober, Sophia
Snijder, Arjan
Ormö, Mats
Strömstedt, Per-Erik
Davies, Rick
Holmberg Schiavone, Lovisa
author_facet Ding, Mei
Tegel, Hanna
Sivertsson, Åsa
Hober, Sophia
Snijder, Arjan
Ormö, Mats
Strömstedt, Per-Erik
Davies, Rick
Holmberg Schiavone, Lovisa
author_sort Ding, Mei
collection PubMed
description Secreted proteins and their cognate plasma membrane receptors regulate human physiology by transducing signals from the extracellular environment into cells resulting in different cellular phenotypes. Systematic use of secretome proteins in assays enables discovery of novel biology and signaling pathways. Several secretome-based phenotypic screening platforms have been described in the literature and shown to facilitate target identification in drug discovery. In this review, we summarize the current status of secretome-based screening. This includes annotation, production, quality control, and sample management of secretome libraries, as well as how secretome libraries have been applied to discover novel target biology using different disease-relevant cell-based assays. A workflow for secretome-based screening is shared based on the AstraZeneca experience. The secretome library offers several advantages compared with other libraries used for target discovery: (1) screening using a secretome library directly identifies the active protein and, in many cases, its cognate receptor, enabling a rapid understanding of the disease pathway and subsequent formation of target hypotheses for drug discovery; (2) the secretome library covers significant areas of biological signaling space, although the size of this library is small; (3) secretome proteins can be added directly to cells without additional manipulation. These factors make the secretome library ideal for testing in physiologically relevant cell types, and therefore it represents an attractive approach to phenotypic target discovery.
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spelling pubmed-73093592020-07-06 Secretome-Based Screening in Target Discovery Ding, Mei Tegel, Hanna Sivertsson, Åsa Hober, Sophia Snijder, Arjan Ormö, Mats Strömstedt, Per-Erik Davies, Rick Holmberg Schiavone, Lovisa SLAS Discov Reviews Secreted proteins and their cognate plasma membrane receptors regulate human physiology by transducing signals from the extracellular environment into cells resulting in different cellular phenotypes. Systematic use of secretome proteins in assays enables discovery of novel biology and signaling pathways. Several secretome-based phenotypic screening platforms have been described in the literature and shown to facilitate target identification in drug discovery. In this review, we summarize the current status of secretome-based screening. This includes annotation, production, quality control, and sample management of secretome libraries, as well as how secretome libraries have been applied to discover novel target biology using different disease-relevant cell-based assays. A workflow for secretome-based screening is shared based on the AstraZeneca experience. The secretome library offers several advantages compared with other libraries used for target discovery: (1) screening using a secretome library directly identifies the active protein and, in many cases, its cognate receptor, enabling a rapid understanding of the disease pathway and subsequent formation of target hypotheses for drug discovery; (2) the secretome library covers significant areas of biological signaling space, although the size of this library is small; (3) secretome proteins can be added directly to cells without additional manipulation. These factors make the secretome library ideal for testing in physiologically relevant cell types, and therefore it represents an attractive approach to phenotypic target discovery. SAGE Publications 2020-05-19 2020-07 /pmc/articles/PMC7309359/ /pubmed/32425085 http://dx.doi.org/10.1177/2472555220917113 Text en © 2020 The Author(s) https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Reviews
Ding, Mei
Tegel, Hanna
Sivertsson, Åsa
Hober, Sophia
Snijder, Arjan
Ormö, Mats
Strömstedt, Per-Erik
Davies, Rick
Holmberg Schiavone, Lovisa
Secretome-Based Screening in Target Discovery
title Secretome-Based Screening in Target Discovery
title_full Secretome-Based Screening in Target Discovery
title_fullStr Secretome-Based Screening in Target Discovery
title_full_unstemmed Secretome-Based Screening in Target Discovery
title_short Secretome-Based Screening in Target Discovery
title_sort secretome-based screening in target discovery
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309359/
https://www.ncbi.nlm.nih.gov/pubmed/32425085
http://dx.doi.org/10.1177/2472555220917113
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