Endoplasmic Reticulum Homeostasis Is Modulated by the Forkhead Transcription Factor FKH-9 During Infection of Caenorhabditis elegans [Cellular Genetics]

Publication Date:
2018-12-07
Publisher:
Genetics Society of America (GSA)
Print ISSN:
0016-6731
Topics:
Biology
Published by:
http://www.genetics-gsa.org/
_version_ 1836399099250737152
autor Tillman, E. J., Richardson, C. E., Cattie, D. J., Reddy, K. C., Lehrbach, N. J., Droste, R., Ruvkun, G., Kim, D. H.
beschreibung Animals have evolved critical mechanisms to maintain cellular and organismal proteostasis during development, disease, and exposure to environmental stressors. The Unfolded Protein Response (UPR) is a conserved pathway that senses and responds to the accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen. We have previously demonstrated that the IRE-1 - XBP-1 branch of the UPR is required to maintain Caenorhabditis elegans ER homeostasis during larval development in the presence of pathogenic Pseudomonas aeruginosa . In this study, we identify loss-of-function mutations in four conserved transcriptional regulators that suppress the larval lethality of xbp-1 mutant animals caused by immune activation in response to infection by pathogenic bacteria: FKH-9 , a forkhead family transcription factor; ARID-1 , an ARID/Bright domain-containing transcription factor; HCF-1 , a transcriptional regulator that associates with histone modifying enzymes; and SIN-3 , a subunit of a histone deacetylase complex. Further characterization of FKH-9 suggests that loss of FKH-9 enhances resistance to the ER toxin tunicamycin and results in enhanced ER-associated degradation (ERAD). Increased ERAD activity of fkh-9 loss-of-function mutants is accompanied by a diminished capacity to degrade cytosolic proteasomal substrates and a corresponding increased sensitivity to the proteasomal inhibitor bortezomib. Our data underscore how the balance between ER and cytosolic proteostasis can be influenced by compensatory activation of ERAD during the physiological ER stress of infection and immune activation.
citation_standardnr 6365903
datenlieferant ipn_articles
feed_id 2584
feed_publisher Genetics Society of America (GSA)
feed_publisher_url http://www.genetics-gsa.org/
insertion_date 2018-12-07
journalissn 0016-6731
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher Genetics Society of America (GSA)
quelle Genetics
relation http://www.genetics.org/cgi/content/short/210/4/1329?rss=1
search_space articles
shingle_author_1 Tillman, E. J., Richardson, C. E., Cattie, D. J., Reddy, K. C., Lehrbach, N. J., Droste, R., Ruvkun, G., Kim, D. H.
shingle_author_2 Tillman, E. J., Richardson, C. E., Cattie, D. J., Reddy, K. C., Lehrbach, N. J., Droste, R., Ruvkun, G., Kim, D. H.
shingle_author_3 Tillman, E. J., Richardson, C. E., Cattie, D. J., Reddy, K. C., Lehrbach, N. J., Droste, R., Ruvkun, G., Kim, D. H.
shingle_author_4 Tillman, E. J., Richardson, C. E., Cattie, D. J., Reddy, K. C., Lehrbach, N. J., Droste, R., Ruvkun, G., Kim, D. H.
shingle_catch_all_1 Endoplasmic Reticulum Homeostasis Is Modulated by the Forkhead Transcription Factor FKH-9 During Infection of Caenorhabditis elegans [Cellular Genetics]
Animals have evolved critical mechanisms to maintain cellular and organismal proteostasis during development, disease, and exposure to environmental stressors. The Unfolded Protein Response (UPR) is a conserved pathway that senses and responds to the accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen. We have previously demonstrated that the IRE-1 - XBP-1 branch of the UPR is required to maintain Caenorhabditis elegans ER homeostasis during larval development in the presence of pathogenic Pseudomonas aeruginosa . In this study, we identify loss-of-function mutations in four conserved transcriptional regulators that suppress the larval lethality of xbp-1 mutant animals caused by immune activation in response to infection by pathogenic bacteria: FKH-9 , a forkhead family transcription factor; ARID-1 , an ARID/Bright domain-containing transcription factor; HCF-1 , a transcriptional regulator that associates with histone modifying enzymes; and SIN-3 , a subunit of a histone deacetylase complex. Further characterization of FKH-9 suggests that loss of FKH-9 enhances resistance to the ER toxin tunicamycin and results in enhanced ER-associated degradation (ERAD). Increased ERAD activity of fkh-9 loss-of-function mutants is accompanied by a diminished capacity to degrade cytosolic proteasomal substrates and a corresponding increased sensitivity to the proteasomal inhibitor bortezomib. Our data underscore how the balance between ER and cytosolic proteostasis can be influenced by compensatory activation of ERAD during the physiological ER stress of infection and immune activation.
Tillman, E. J., Richardson, C. E., Cattie, D. J., Reddy, K. C., Lehrbach, N. J., Droste, R., Ruvkun, G., Kim, D. H.
Genetics Society of America (GSA)
0016-6731
00166731
shingle_catch_all_2 Endoplasmic Reticulum Homeostasis Is Modulated by the Forkhead Transcription Factor FKH-9 During Infection of Caenorhabditis elegans [Cellular Genetics]
Animals have evolved critical mechanisms to maintain cellular and organismal proteostasis during development, disease, and exposure to environmental stressors. The Unfolded Protein Response (UPR) is a conserved pathway that senses and responds to the accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen. We have previously demonstrated that the IRE-1 - XBP-1 branch of the UPR is required to maintain Caenorhabditis elegans ER homeostasis during larval development in the presence of pathogenic Pseudomonas aeruginosa . In this study, we identify loss-of-function mutations in four conserved transcriptional regulators that suppress the larval lethality of xbp-1 mutant animals caused by immune activation in response to infection by pathogenic bacteria: FKH-9 , a forkhead family transcription factor; ARID-1 , an ARID/Bright domain-containing transcription factor; HCF-1 , a transcriptional regulator that associates with histone modifying enzymes; and SIN-3 , a subunit of a histone deacetylase complex. Further characterization of FKH-9 suggests that loss of FKH-9 enhances resistance to the ER toxin tunicamycin and results in enhanced ER-associated degradation (ERAD). Increased ERAD activity of fkh-9 loss-of-function mutants is accompanied by a diminished capacity to degrade cytosolic proteasomal substrates and a corresponding increased sensitivity to the proteasomal inhibitor bortezomib. Our data underscore how the balance between ER and cytosolic proteostasis can be influenced by compensatory activation of ERAD during the physiological ER stress of infection and immune activation.
Tillman, E. J., Richardson, C. E., Cattie, D. J., Reddy, K. C., Lehrbach, N. J., Droste, R., Ruvkun, G., Kim, D. H.
Genetics Society of America (GSA)
0016-6731
00166731
shingle_catch_all_3 Endoplasmic Reticulum Homeostasis Is Modulated by the Forkhead Transcription Factor FKH-9 During Infection of Caenorhabditis elegans [Cellular Genetics]
Animals have evolved critical mechanisms to maintain cellular and organismal proteostasis during development, disease, and exposure to environmental stressors. The Unfolded Protein Response (UPR) is a conserved pathway that senses and responds to the accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen. We have previously demonstrated that the IRE-1 - XBP-1 branch of the UPR is required to maintain Caenorhabditis elegans ER homeostasis during larval development in the presence of pathogenic Pseudomonas aeruginosa . In this study, we identify loss-of-function mutations in four conserved transcriptional regulators that suppress the larval lethality of xbp-1 mutant animals caused by immune activation in response to infection by pathogenic bacteria: FKH-9 , a forkhead family transcription factor; ARID-1 , an ARID/Bright domain-containing transcription factor; HCF-1 , a transcriptional regulator that associates with histone modifying enzymes; and SIN-3 , a subunit of a histone deacetylase complex. Further characterization of FKH-9 suggests that loss of FKH-9 enhances resistance to the ER toxin tunicamycin and results in enhanced ER-associated degradation (ERAD). Increased ERAD activity of fkh-9 loss-of-function mutants is accompanied by a diminished capacity to degrade cytosolic proteasomal substrates and a corresponding increased sensitivity to the proteasomal inhibitor bortezomib. Our data underscore how the balance between ER and cytosolic proteostasis can be influenced by compensatory activation of ERAD during the physiological ER stress of infection and immune activation.
Tillman, E. J., Richardson, C. E., Cattie, D. J., Reddy, K. C., Lehrbach, N. J., Droste, R., Ruvkun, G., Kim, D. H.
Genetics Society of America (GSA)
0016-6731
00166731
shingle_catch_all_4 Endoplasmic Reticulum Homeostasis Is Modulated by the Forkhead Transcription Factor FKH-9 During Infection of Caenorhabditis elegans [Cellular Genetics]
Animals have evolved critical mechanisms to maintain cellular and organismal proteostasis during development, disease, and exposure to environmental stressors. The Unfolded Protein Response (UPR) is a conserved pathway that senses and responds to the accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen. We have previously demonstrated that the IRE-1 - XBP-1 branch of the UPR is required to maintain Caenorhabditis elegans ER homeostasis during larval development in the presence of pathogenic Pseudomonas aeruginosa . In this study, we identify loss-of-function mutations in four conserved transcriptional regulators that suppress the larval lethality of xbp-1 mutant animals caused by immune activation in response to infection by pathogenic bacteria: FKH-9 , a forkhead family transcription factor; ARID-1 , an ARID/Bright domain-containing transcription factor; HCF-1 , a transcriptional regulator that associates with histone modifying enzymes; and SIN-3 , a subunit of a histone deacetylase complex. Further characterization of FKH-9 suggests that loss of FKH-9 enhances resistance to the ER toxin tunicamycin and results in enhanced ER-associated degradation (ERAD). Increased ERAD activity of fkh-9 loss-of-function mutants is accompanied by a diminished capacity to degrade cytosolic proteasomal substrates and a corresponding increased sensitivity to the proteasomal inhibitor bortezomib. Our data underscore how the balance between ER and cytosolic proteostasis can be influenced by compensatory activation of ERAD during the physiological ER stress of infection and immune activation.
Tillman, E. J., Richardson, C. E., Cattie, D. J., Reddy, K. C., Lehrbach, N. J., Droste, R., Ruvkun, G., Kim, D. H.
Genetics Society of America (GSA)
0016-6731
00166731
shingle_title_1 Endoplasmic Reticulum Homeostasis Is Modulated by the Forkhead Transcription Factor FKH-9 During Infection of Caenorhabditis elegans [Cellular Genetics]
shingle_title_2 Endoplasmic Reticulum Homeostasis Is Modulated by the Forkhead Transcription Factor FKH-9 During Infection of Caenorhabditis elegans [Cellular Genetics]
shingle_title_3 Endoplasmic Reticulum Homeostasis Is Modulated by the Forkhead Transcription Factor FKH-9 During Infection of Caenorhabditis elegans [Cellular Genetics]
shingle_title_4 Endoplasmic Reticulum Homeostasis Is Modulated by the Forkhead Transcription Factor FKH-9 During Infection of Caenorhabditis elegans [Cellular Genetics]
timestamp 2025-06-30T23:37:35.338Z
titel Endoplasmic Reticulum Homeostasis Is Modulated by the Forkhead Transcription Factor FKH-9 During Infection of Caenorhabditis elegans [Cellular Genetics]
titel_suche Endoplasmic Reticulum Homeostasis Is Modulated by the Forkhead Transcription Factor FKH-9 During Infection of Caenorhabditis elegans [Cellular Genetics]
topic W
uid ipn_articles_6365903