Ubiquitin receptors are required for substrate-mediated activation of the proteasome’s unfolding ability

Abstract The ubiquitin-proteasome system (UPS) is responsible for the bulk of protein degradation in eukaryotic cells, but the factors that cause different substrates to be unfolded and degraded to different extents are still poorly understood. We previously showed that polyubiquitinated substrates...

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Autores principales:	Mary D. Cundiff, Christina M. Hurley, Jeremy D. Wong, Joseph A. Boscia, Aarti Bashyal, Jake Rosenberg, Eden L. Reichard, Nicholas D. Nassif, Jennifer S. Brodbelt, Daniel A. Kraut
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/88efcdeee9f84f3485e5d78c2f85812e
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spelling	oai:doaj.org-article:88efcdeee9f84f3485e5d78c2f85812e2021-12-02T15:09:42ZUbiquitin receptors are required for substrate-mediated activation of the proteasome’s unfolding ability10.1038/s41598-019-50857-y2045-2322https://doaj.org/article/88efcdeee9f84f3485e5d78c2f85812e2019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50857-yhttps://doaj.org/toc/2045-2322Abstract The ubiquitin-proteasome system (UPS) is responsible for the bulk of protein degradation in eukaryotic cells, but the factors that cause different substrates to be unfolded and degraded to different extents are still poorly understood. We previously showed that polyubiquitinated substrates were degraded with greater processivity (with a higher tendency to be unfolded and degraded than released) than ubiquitin-independent substrates. Thus, even though ubiquitin chains are removed before unfolding and degradation occur, they affect the unfolding of a protein domain. How do ubiquitin chains activate the proteasome’s unfolding ability? We investigated the roles of the three intrinsic proteasomal ubiquitin receptors - Rpn1, Rpn10 and Rpn13 - in this activation. We find that these receptors are required for substrate-mediated activation of the proteasome’s unfolding ability. Rpn13 plays the largest role, but there is also partial redundancy between receptors. The architecture of substrate ubiquitination determines which receptors are needed for maximal unfolding ability, and, in some cases, simultaneous engagement of ubiquitin by multiple receptors may be required. Our results suggest physical models for how ubiquitin receptors communicate with the proteasomal motor proteins.Mary D. CundiffChristina M. HurleyJeremy D. WongJoseph A. BosciaAarti BashyalJake RosenbergEden L. ReichardNicholas D. NassifJennifer S. BrodbeltDaniel A. KrautNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-17 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mary D. Cundiff Christina M. Hurley Jeremy D. Wong Joseph A. Boscia Aarti Bashyal Jake Rosenberg Eden L. Reichard Nicholas D. Nassif Jennifer S. Brodbelt Daniel A. Kraut Ubiquitin receptors are required for substrate-mediated activation of the proteasome’s unfolding ability
description	Abstract The ubiquitin-proteasome system (UPS) is responsible for the bulk of protein degradation in eukaryotic cells, but the factors that cause different substrates to be unfolded and degraded to different extents are still poorly understood. We previously showed that polyubiquitinated substrates were degraded with greater processivity (with a higher tendency to be unfolded and degraded than released) than ubiquitin-independent substrates. Thus, even though ubiquitin chains are removed before unfolding and degradation occur, they affect the unfolding of a protein domain. How do ubiquitin chains activate the proteasome’s unfolding ability? We investigated the roles of the three intrinsic proteasomal ubiquitin receptors - Rpn1, Rpn10 and Rpn13 - in this activation. We find that these receptors are required for substrate-mediated activation of the proteasome’s unfolding ability. Rpn13 plays the largest role, but there is also partial redundancy between receptors. The architecture of substrate ubiquitination determines which receptors are needed for maximal unfolding ability, and, in some cases, simultaneous engagement of ubiquitin by multiple receptors may be required. Our results suggest physical models for how ubiquitin receptors communicate with the proteasomal motor proteins.
format	article
author	Mary D. Cundiff Christina M. Hurley Jeremy D. Wong Joseph A. Boscia Aarti Bashyal Jake Rosenberg Eden L. Reichard Nicholas D. Nassif Jennifer S. Brodbelt Daniel A. Kraut
author_facet	Mary D. Cundiff Christina M. Hurley Jeremy D. Wong Joseph A. Boscia Aarti Bashyal Jake Rosenberg Eden L. Reichard Nicholas D. Nassif Jennifer S. Brodbelt Daniel A. Kraut
author_sort	Mary D. Cundiff
title	Ubiquitin receptors are required for substrate-mediated activation of the proteasome’s unfolding ability
title_short	Ubiquitin receptors are required for substrate-mediated activation of the proteasome’s unfolding ability
title_full	Ubiquitin receptors are required for substrate-mediated activation of the proteasome’s unfolding ability
title_fullStr	Ubiquitin receptors are required for substrate-mediated activation of the proteasome’s unfolding ability
title_full_unstemmed	Ubiquitin receptors are required for substrate-mediated activation of the proteasome’s unfolding ability
title_sort	ubiquitin receptors are required for substrate-mediated activation of the proteasome’s unfolding ability
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/88efcdeee9f84f3485e5d78c2f85812e
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Ubiquitin receptors are required for substrate-mediated activation of the proteasome’s unfolding ability

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