20S immunoproteasomes remove formaldehyde-damaged cytoplasmic proteins suppressing caspase-independent cell death

Abstract Immunoproteasomes are known for their involvement in antigen presentation. However, their broad tissue presence and other evidence are indicative of nonimmune functions. We examined a role for immunoproteasomes in cellular responses to the endogenous and environmental carcinogen formaldehyd...

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Autores principales:	Sara Ortega-Atienza, Casey Krawic, Lauren Watts, Caitlin McCarthy, Michal W. Luczak, Anatoly Zhitkovich
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/19f101b59bc04e38be53c554606594ca
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spelling	oai:doaj.org-article:19f101b59bc04e38be53c554606594ca2021-12-02T11:40:43Z20S immunoproteasomes remove formaldehyde-damaged cytoplasmic proteins suppressing caspase-independent cell death10.1038/s41598-017-00757-w2045-2322https://doaj.org/article/19f101b59bc04e38be53c554606594ca2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00757-whttps://doaj.org/toc/2045-2322Abstract Immunoproteasomes are known for their involvement in antigen presentation. However, their broad tissue presence and other evidence are indicative of nonimmune functions. We examined a role for immunoproteasomes in cellular responses to the endogenous and environmental carcinogen formaldehyde (FA) that binds to cytosolic and nuclear proteins producing proteotoxic stress and genotoxic DNA-histone crosslinks. We found that immunoproteasomes were important for suppression of a caspase-independent cell death and the long-term survival of FA-treated cells. All major genotoxic responses to FA, including replication inhibition and activation of the transcription factor p53 and the apical ATM and ATR kinases, were unaffected by immunoproteasome inactivity. Immunoproteasome inhibition enhanced activation of the cytosolic protein damage sensor HSF1, elevated levels of K48-polyubiquitinated cytoplasmic proteins and increased depletion of unconjugated ubiquitin. We further found that FA induced the disassembly of 26S immunoproteasomes, but not standard 26S proteasomes, releasing the 20S catalytic immunoproteasome. FA-treated cells also had higher amounts of small activators PA28αβ and PA28γ bound to 20S particles. Our findings highlight the significance of nonnuclear damage in FA injury and reveal a major role for immunoproteasomes in elimination of FA-damaged cytoplasmic proteins through ubiquitin-independent proteolysis.Sara Ortega-AtienzaCasey KrawicLauren WattsCaitlin McCarthyMichal W. LuczakAnatoly ZhitkovichNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sara Ortega-Atienza Casey Krawic Lauren Watts Caitlin McCarthy Michal W. Luczak Anatoly Zhitkovich 20S immunoproteasomes remove formaldehyde-damaged cytoplasmic proteins suppressing caspase-independent cell death
description	Abstract Immunoproteasomes are known for their involvement in antigen presentation. However, their broad tissue presence and other evidence are indicative of nonimmune functions. We examined a role for immunoproteasomes in cellular responses to the endogenous and environmental carcinogen formaldehyde (FA) that binds to cytosolic and nuclear proteins producing proteotoxic stress and genotoxic DNA-histone crosslinks. We found that immunoproteasomes were important for suppression of a caspase-independent cell death and the long-term survival of FA-treated cells. All major genotoxic responses to FA, including replication inhibition and activation of the transcription factor p53 and the apical ATM and ATR kinases, were unaffected by immunoproteasome inactivity. Immunoproteasome inhibition enhanced activation of the cytosolic protein damage sensor HSF1, elevated levels of K48-polyubiquitinated cytoplasmic proteins and increased depletion of unconjugated ubiquitin. We further found that FA induced the disassembly of 26S immunoproteasomes, but not standard 26S proteasomes, releasing the 20S catalytic immunoproteasome. FA-treated cells also had higher amounts of small activators PA28αβ and PA28γ bound to 20S particles. Our findings highlight the significance of nonnuclear damage in FA injury and reveal a major role for immunoproteasomes in elimination of FA-damaged cytoplasmic proteins through ubiquitin-independent proteolysis.
format	article
author	Sara Ortega-Atienza Casey Krawic Lauren Watts Caitlin McCarthy Michal W. Luczak Anatoly Zhitkovich
author_facet	Sara Ortega-Atienza Casey Krawic Lauren Watts Caitlin McCarthy Michal W. Luczak Anatoly Zhitkovich
author_sort	Sara Ortega-Atienza
title	20S immunoproteasomes remove formaldehyde-damaged cytoplasmic proteins suppressing caspase-independent cell death
title_short	20S immunoproteasomes remove formaldehyde-damaged cytoplasmic proteins suppressing caspase-independent cell death
title_full	20S immunoproteasomes remove formaldehyde-damaged cytoplasmic proteins suppressing caspase-independent cell death
title_fullStr	20S immunoproteasomes remove formaldehyde-damaged cytoplasmic proteins suppressing caspase-independent cell death
title_full_unstemmed	20S immunoproteasomes remove formaldehyde-damaged cytoplasmic proteins suppressing caspase-independent cell death
title_sort	20s immunoproteasomes remove formaldehyde-damaged cytoplasmic proteins suppressing caspase-independent cell death
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/19f101b59bc04e38be53c554606594ca
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20S immunoproteasomes remove formaldehyde-damaged cytoplasmic proteins suppressing caspase-independent cell death

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