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The CBP-1/p300 Lysine Acetyltransferase Regulates the Heat Shock Response in C. elegans

The decline of proteostasis is a hallmark of aging that is, in part, affected by the dysregulation of the heat shock response (HSR), a highly conserved cellular response to proteotoxic stress in the cell. The heat shock transcription factor HSF-1 is well-studied as a key regulator of proteostasis, b...

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Autores principales: Barrett, Lindsey N., Westerheide, Sandy D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261439/
https://www.ncbi.nlm.nih.gov/pubmed/35821825
http://dx.doi.org/10.3389/fragi.2022.861761
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author Barrett, Lindsey N.
Westerheide, Sandy D.
author_facet Barrett, Lindsey N.
Westerheide, Sandy D.
author_sort Barrett, Lindsey N.
collection PubMed
description The decline of proteostasis is a hallmark of aging that is, in part, affected by the dysregulation of the heat shock response (HSR), a highly conserved cellular response to proteotoxic stress in the cell. The heat shock transcription factor HSF-1 is well-studied as a key regulator of proteostasis, but mechanisms that could be used to modulate HSF-1 function to enhance proteostasis during aging are largely unknown. In this study, we examined lysine acetyltransferase regulation of the HSR and HSF-1 in C. elegans. We performed an RNA interference screen of lysine acetyltransferases and examined mRNA expression of the heat-shock inducible gene hsp-16.2, a widely used marker for HSR activation. From this screen, we identified one acetyltransferase, CBP-1, the C. elegans homolog of mammalian CREB-binding protein CBP/p300, as a negative regulator of the HSR. We found that while knockdown of CBP-1 decreases the overall lifespan of the worm, it also enhances heat shock protein production upon heat shock and increases thermotolerance of the worm in an HSF-1 dependent manner. Similarly, we examined a hallmark of HSF-1 activation, the formation of nuclear stress bodies (nSBs). In analyzing the recovery rate of nSBs, we found that knockdown of CBP-1 enhanced the recovery and resolution of nSBs after stress. Collectively, our studies demonstrate a role of CBP-1 as a negative regulator of HSF-1 activity and its physiological effects at the organismal level upon stress.
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spelling pubmed-92614392022-07-11 The CBP-1/p300 Lysine Acetyltransferase Regulates the Heat Shock Response in C. elegans Barrett, Lindsey N. Westerheide, Sandy D. Front Aging Aging The decline of proteostasis is a hallmark of aging that is, in part, affected by the dysregulation of the heat shock response (HSR), a highly conserved cellular response to proteotoxic stress in the cell. The heat shock transcription factor HSF-1 is well-studied as a key regulator of proteostasis, but mechanisms that could be used to modulate HSF-1 function to enhance proteostasis during aging are largely unknown. In this study, we examined lysine acetyltransferase regulation of the HSR and HSF-1 in C. elegans. We performed an RNA interference screen of lysine acetyltransferases and examined mRNA expression of the heat-shock inducible gene hsp-16.2, a widely used marker for HSR activation. From this screen, we identified one acetyltransferase, CBP-1, the C. elegans homolog of mammalian CREB-binding protein CBP/p300, as a negative regulator of the HSR. We found that while knockdown of CBP-1 decreases the overall lifespan of the worm, it also enhances heat shock protein production upon heat shock and increases thermotolerance of the worm in an HSF-1 dependent manner. Similarly, we examined a hallmark of HSF-1 activation, the formation of nuclear stress bodies (nSBs). In analyzing the recovery rate of nSBs, we found that knockdown of CBP-1 enhanced the recovery and resolution of nSBs after stress. Collectively, our studies demonstrate a role of CBP-1 as a negative regulator of HSF-1 activity and its physiological effects at the organismal level upon stress. Frontiers Media S.A. 2022-04-27 /pmc/articles/PMC9261439/ /pubmed/35821825 http://dx.doi.org/10.3389/fragi.2022.861761 Text en Copyright © 2022 Barrett and Westerheide. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Aging
Barrett, Lindsey N.
Westerheide, Sandy D.
The CBP-1/p300 Lysine Acetyltransferase Regulates the Heat Shock Response in C. elegans
title The CBP-1/p300 Lysine Acetyltransferase Regulates the Heat Shock Response in C. elegans
title_full The CBP-1/p300 Lysine Acetyltransferase Regulates the Heat Shock Response in C. elegans
title_fullStr The CBP-1/p300 Lysine Acetyltransferase Regulates the Heat Shock Response in C. elegans
title_full_unstemmed The CBP-1/p300 Lysine Acetyltransferase Regulates the Heat Shock Response in C. elegans
title_short The CBP-1/p300 Lysine Acetyltransferase Regulates the Heat Shock Response in C. elegans
title_sort cbp-1/p300 lysine acetyltransferase regulates the heat shock response in c. elegans
topic Aging
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261439/
https://www.ncbi.nlm.nih.gov/pubmed/35821825
http://dx.doi.org/10.3389/fragi.2022.861761
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