Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway

Proteins targeted to the secretory pathway start their intracellular journey by being transported across biological membranes such as the endoplasmic reticulum (ER). A central component in this protein translocation process across the ER is the Sec61 translocon complex, which is only intracellularly...

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Autores principales:	Eva Pauwels, Ralf Schülein, Kurt Vermeire
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	signal recognition particle dependent protein targeting Sec61 dependent translocation co-translational translocation endoplasmic reticulum inhibitor high throughput screening Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/adcbc969cd514f42adfb7fd09346c4e8
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spelling	oai:doaj.org-article:adcbc969cd514f42adfb7fd09346c4e82021-11-11T17:25:37ZInhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway10.3390/ijms2221120071422-00671661-6596https://doaj.org/article/adcbc969cd514f42adfb7fd09346c4e82021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12007https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Proteins targeted to the secretory pathway start their intracellular journey by being transported across biological membranes such as the endoplasmic reticulum (ER). A central component in this protein translocation process across the ER is the Sec61 translocon complex, which is only intracellularly expressed and does not have any enzymatic activity. In addition, Sec61 translocon complexes are difficult to purify and to reconstitute. Screening for small molecule inhibitors impairing its function has thus been notoriously difficult. However, such translocation inhibitors may not only be valuable tools for cell biology, but may also represent novel anticancer drugs, given that cancer cells heavily depend on efficient protein translocation into the ER to support their fast growth. In this review, different inhibitors of protein translocation will be discussed, and their specific mode of action will be compared. In addition, recently published screening strategies for small molecule inhibitors targeting the whole SRP-Sec61 targeting/translocation pathway will be summarized. Of note, slightly modified assays may be used in the future to screen for substances affecting SecYEG, the bacterial ortholog of the Sec61 complex, in order to identify novel antibiotic drugs.Eva PauwelsRalf SchüleinKurt VermeireMDPI AGarticlesignal recognition particle dependent protein targetingSec61 dependent translocationco-translational translocationendoplasmic reticuluminhibitorhigh throughput screeningBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12007, p 12007 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	signal recognition particle dependent protein targeting Sec61 dependent translocation co-translational translocation endoplasmic reticulum inhibitor high throughput screening Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	signal recognition particle dependent protein targeting Sec61 dependent translocation co-translational translocation endoplasmic reticulum inhibitor high throughput screening Biology (General) QH301-705.5 Chemistry QD1-999 Eva Pauwels Ralf Schülein Kurt Vermeire Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway
description	Proteins targeted to the secretory pathway start their intracellular journey by being transported across biological membranes such as the endoplasmic reticulum (ER). A central component in this protein translocation process across the ER is the Sec61 translocon complex, which is only intracellularly expressed and does not have any enzymatic activity. In addition, Sec61 translocon complexes are difficult to purify and to reconstitute. Screening for small molecule inhibitors impairing its function has thus been notoriously difficult. However, such translocation inhibitors may not only be valuable tools for cell biology, but may also represent novel anticancer drugs, given that cancer cells heavily depend on efficient protein translocation into the ER to support their fast growth. In this review, different inhibitors of protein translocation will be discussed, and their specific mode of action will be compared. In addition, recently published screening strategies for small molecule inhibitors targeting the whole SRP-Sec61 targeting/translocation pathway will be summarized. Of note, slightly modified assays may be used in the future to screen for substances affecting SecYEG, the bacterial ortholog of the Sec61 complex, in order to identify novel antibiotic drugs.
format	article
author	Eva Pauwels Ralf Schülein Kurt Vermeire
author_facet	Eva Pauwels Ralf Schülein Kurt Vermeire
author_sort	Eva Pauwels
title	Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway
title_short	Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway
title_full	Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway
title_fullStr	Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway
title_full_unstemmed	Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway
title_sort	inhibitors of the sec61 complex and novel high throughput screening strategies to target the protein translocation pathway
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/adcbc969cd514f42adfb7fd09346c4e8
work_keys_str_mv	AT evapauwels inhibitorsofthesec61complexandnovelhighthroughputscreeningstrategiestotargettheproteintranslocationpathway AT ralfschulein inhibitorsofthesec61complexandnovelhighthroughputscreeningstrategiestotargettheproteintranslocationpathway AT kurtvermeire inhibitorsofthesec61complexandnovelhighthroughputscreeningstrategiestotargettheproteintranslocationpathway
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Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway

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