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An Arsenite Relay between PSMD14 and AIRAP Enables Revival of Proteasomal DUB Activity

Maintaining 26S proteasome activity under diverse physiological conditions is a fundamental requirement in order to maintain cellular proteostasis. Several quantitative and qualitative mechanisms have evolved to ensure that ubiquitin–proteasome system (UPS) substrates do not accumulate and lead to p...

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Detalles Bibliográficos
Autores principales: Sukenik, Sigalit, Braunstein, Ilana, Stanhill, Ariel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465394/
https://www.ncbi.nlm.nih.gov/pubmed/34572530
http://dx.doi.org/10.3390/biom11091317
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author Sukenik, Sigalit
Braunstein, Ilana
Stanhill, Ariel
author_facet Sukenik, Sigalit
Braunstein, Ilana
Stanhill, Ariel
author_sort Sukenik, Sigalit
collection PubMed
description Maintaining 26S proteasome activity under diverse physiological conditions is a fundamental requirement in order to maintain cellular proteostasis. Several quantitative and qualitative mechanisms have evolved to ensure that ubiquitin–proteasome system (UPS) substrates do not accumulate and lead to promiscuous protein–protein interactions that, in turn, lead to cellular malfunction. In this report, we demonstrate that Arsenite Inducible Regulatory Particle-Associate Protein (AIRAP), previously reported as a proteasomal adaptor required for maintaining proteasomal flux during arsenite exposure, can directly bind arsenite molecules. We further show that arsenite inhibits Psmd14/Rpn11 metalloprotease deubiquitination activity by substituting zinc binding to the MPN/JAMM domain. The proteasomal adaptor AIRAP is able to directly relieve PSMD14/Rpn11 inhibition. A possible metal relay between arsenylated PSMD14/Rpn11 and AIRAP may serve as a cellular mechanism that senses proteasomal inhibition to restore Psmd14/Rpn11 activity.
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spelling pubmed-84653942021-09-27 An Arsenite Relay between PSMD14 and AIRAP Enables Revival of Proteasomal DUB Activity Sukenik, Sigalit Braunstein, Ilana Stanhill, Ariel Biomolecules Article Maintaining 26S proteasome activity under diverse physiological conditions is a fundamental requirement in order to maintain cellular proteostasis. Several quantitative and qualitative mechanisms have evolved to ensure that ubiquitin–proteasome system (UPS) substrates do not accumulate and lead to promiscuous protein–protein interactions that, in turn, lead to cellular malfunction. In this report, we demonstrate that Arsenite Inducible Regulatory Particle-Associate Protein (AIRAP), previously reported as a proteasomal adaptor required for maintaining proteasomal flux during arsenite exposure, can directly bind arsenite molecules. We further show that arsenite inhibits Psmd14/Rpn11 metalloprotease deubiquitination activity by substituting zinc binding to the MPN/JAMM domain. The proteasomal adaptor AIRAP is able to directly relieve PSMD14/Rpn11 inhibition. A possible metal relay between arsenylated PSMD14/Rpn11 and AIRAP may serve as a cellular mechanism that senses proteasomal inhibition to restore Psmd14/Rpn11 activity. MDPI 2021-09-06 /pmc/articles/PMC8465394/ /pubmed/34572530 http://dx.doi.org/10.3390/biom11091317 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sukenik, Sigalit
Braunstein, Ilana
Stanhill, Ariel
An Arsenite Relay between PSMD14 and AIRAP Enables Revival of Proteasomal DUB Activity
title An Arsenite Relay between PSMD14 and AIRAP Enables Revival of Proteasomal DUB Activity
title_full An Arsenite Relay between PSMD14 and AIRAP Enables Revival of Proteasomal DUB Activity
title_fullStr An Arsenite Relay between PSMD14 and AIRAP Enables Revival of Proteasomal DUB Activity
title_full_unstemmed An Arsenite Relay between PSMD14 and AIRAP Enables Revival of Proteasomal DUB Activity
title_short An Arsenite Relay between PSMD14 and AIRAP Enables Revival of Proteasomal DUB Activity
title_sort arsenite relay between psmd14 and airap enables revival of proteasomal dub activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465394/
https://www.ncbi.nlm.nih.gov/pubmed/34572530
http://dx.doi.org/10.3390/biom11091317
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