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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8465394 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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