Impact of histone deacetylase inhibition and arimoclomol on heat shock protein expression and disease biomarkers in primary culture models of familial ALS
This study compared expression of these HSPs in cultured motor neurons expressing three variants linked to familial ALS: TDP-43G348C, FUSR521G or SOD1G93A. All variants were poor inducers of Hspa1a, and reduced levels of Hspa8 mRNA and protein, indicating multiple compromises in chaperoning capacity. To promote HSP expression, cultures were treated with the putative HSP co-inducer, arimoclomol, class I histone deacetylase (HDAC) inhibitors to promote active chromatin for transcription, and the combination. Treatments had variable, often different effects on expression of Hspa1a and Hspa8, depending on the ALS variant expre...
Source: Cell Stress and Chaperones - April 3, 2024 Category: Cytology Authors: Mario Fern ández Comaduran Sandra Minotti Suleima Jacob-Tomas Javeria Rizwan Nancy Larochelle Richard Robitaille Chantelle F Sephton M Vera Josephine N Nalbantoglu Heather D Durham Source Type: research
Impact of histone deacetylase inhibition and arimoclomol on heat shock protein expression and disease biomarkers in primary culture models of familial ALS
This study compared expression of these HSPs in cultured motor neurons expressing three variants linked to familial ALS: TDP-43G348C, FUSR521G or SOD1G93A. All variants were poor inducers of Hspa1a, and reduced levels of Hspa8 mRNA and protein, indicating multiple compromises in chaperoning capacity. To promote HSP expression, cultures were treated with the putative HSP co-inducer, arimoclomol, class I histone deacetylase (HDAC) inhibitors to promote active chromatin for transcription, and the combination. Treatments had variable, often different effects on expression of Hspa1a and Hspa8, depending on the ALS variant expre...
Source: Cell Stress and Chaperones - April 3, 2024 Category: Cytology Authors: Mario Fern ández Comaduran Sandra Minotti Suleima Jacob-Tomas Javeria Rizwan Nancy Larochelle Richard Robitaille Chantelle F Sephton M Vera Josephine N Nalbantoglu Heather D Durham Source Type: research
Autorepression of yeast Hsp70 cochaperones by intramolecular interactions involving their J-domains
Cell Stress Chaperones. 2024 Mar 21;29(2):338-348. doi: 10.1016/j.cstres.2024.03.008. Online ahead of print.ABSTRACTThe 70 kDa heat shock protein (Hsp70) chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) coevolved with Hsp70s to trigger ATP hydrolysis and catalytically upload various substrate polypeptides in need to be structurally modified by the chaperone. Here, we measured the protein disaggregation and refolding activities of the main yeast cytosolic Hsp70, Ssa1, in the presence of its most abundant JDPs, Sis1 and Ydj1, and two swap mutants, in which the J-dom...
Source: Cell Stress and Chaperones - March 23, 2024 Category: Cytology Authors: Mathieu E Rebeaud Satyam Tiwari Bruno Fauvet Adela ïde Mohr Pierre Goloubinoff Paolo De Los Rios Source Type: research
Autorepression of Yeast Hsp70 co-chaperones by intramolecular interactions involving their J-domains
Cell Stress Chaperones. 2024 Mar 21:S1355-8145(24)00060-9. doi: 10.1016/j.cstres.2024.03.008. Online ahead of print.ABSTRACTThe Hsp70 chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) co-evolved with Hsp70s to trigger ATP-hydrolysis and catalytically upload various substrate polypeptides in need to be structurally modified by the chaperone. Here, we measured the protein disaggregation and refolding activities of the main yeast cytosolic Hsp70, Ssa1, in the presence of its most abundant JDPs, Sis1 and Ydj1, and two swap mutants, in which the J-domains have been inte...
Source: Cell Stress and Chaperones - March 23, 2024 Category: Cytology Authors: Mathieu E Rebeaud Satyam Tiwari Bruno Fauvet Adela ïde Mohr Paolo De Los Rios Pierre Goloubinoff Source Type: research
Autorepression of Yeast Hsp70 co-chaperones by intramolecular interactions involving their J-domains
Cell Stress Chaperones. 2024 Mar 21:S1355-8145(24)00060-9. doi: 10.1016/j.cstres.2024.03.008. Online ahead of print.ABSTRACTThe Hsp70 chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) co-evolved with Hsp70s to trigger ATP-hydrolysis and catalytically upload various substrate polypeptides in need to be structurally modified by the chaperone. Here, we measured the protein disaggregation and refolding activities of the main yeast cytosolic Hsp70, Ssa1, in the presence of its most abundant JDPs, Sis1 and Ydj1, and two swap mutants, in which the J-domains have been inte...
Source: Cell Stress and Chaperones - March 23, 2024 Category: Cytology Authors: Mathieu E Rebeaud Satyam Tiwari Bruno Fauvet Adela ïde Mohr Paolo De Los Rios Pierre Goloubinoff Source Type: research
Autorepression of Yeast Hsp70 co-chaperones by intramolecular interactions involving their J-domains
Cell Stress Chaperones. 2024 Mar 21:S1355-8145(24)00060-9. doi: 10.1016/j.cstres.2024.03.008. Online ahead of print.ABSTRACTThe Hsp70 chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) co-evolved with Hsp70s to trigger ATP-hydrolysis and catalytically upload various substrate polypeptides in need to be structurally modified by the chaperone. Here, we measured the protein disaggregation and refolding activities of the main yeast cytosolic Hsp70, Ssa1, in the presence of its most abundant JDPs, Sis1 and Ydj1, and two swap mutants, in which the J-domains have been inte...
Source: Cell Stress and Chaperones - March 23, 2024 Category: Cytology Authors: Mathieu E Rebeaud Satyam Tiwari Bruno Fauvet Adela ïde Mohr Paolo De Los Rios Pierre Goloubinoff Source Type: research
Autorepression of Yeast Hsp70 co-chaperones by intramolecular interactions involving their J-domains
Cell Stress Chaperones. 2024 Mar 21:S1355-8145(24)00060-9. doi: 10.1016/j.cstres.2024.03.008. Online ahead of print.ABSTRACTThe Hsp70 chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) co-evolved with Hsp70s to trigger ATP-hydrolysis and catalytically upload various substrate polypeptides in need to be structurally modified by the chaperone. Here, we measured the protein disaggregation and refolding activities of the main yeast cytosolic Hsp70, Ssa1, in the presence of its most abundant JDPs, Sis1 and Ydj1, and two swap mutants, in which the J-domains have been inte...
Source: Cell Stress and Chaperones - March 23, 2024 Category: Cytology Authors: Mathieu E Rebeaud Satyam Tiwari Bruno Fauvet Adela ïde Mohr Paolo De Los Rios Pierre Goloubinoff Source Type: research
Autorepression of Yeast Hsp70 co-chaperones by intramolecular interactions involving their J-domains
Cell Stress Chaperones. 2024 Mar 21:S1355-8145(24)00060-9. doi: 10.1016/j.cstres.2024.03.008. Online ahead of print.ABSTRACTThe Hsp70 chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) co-evolved with Hsp70s to trigger ATP-hydrolysis and catalytically upload various substrate polypeptides in need to be structurally modified by the chaperone. Here, we measured the protein disaggregation and refolding activities of the main yeast cytosolic Hsp70, Ssa1, in the presence of its most abundant JDPs, Sis1 and Ydj1, and two swap mutants, in which the J-domains have been inte...
Source: Cell Stress and Chaperones - March 23, 2024 Category: Cytology Authors: Mathieu E Rebeaud Satyam Tiwari Bruno Fauvet Adela ïde Mohr Paolo De Los Rios Pierre Goloubinoff Source Type: research
Autorepression of Yeast Hsp70 co-chaperones by intramolecular interactions involving their J-domains
Cell Stress Chaperones. 2024 Mar 21:S1355-8145(24)00060-9. doi: 10.1016/j.cstres.2024.03.008. Online ahead of print.ABSTRACTThe Hsp70 chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) co-evolved with Hsp70s to trigger ATP-hydrolysis and catalytically upload various substrate polypeptides in need to be structurally modified by the chaperone. Here, we measured the protein disaggregation and refolding activities of the main yeast cytosolic Hsp70, Ssa1, in the presence of its most abundant JDPs, Sis1 and Ydj1, and two swap mutants, in which the J-domains have been inte...
Source: Cell Stress and Chaperones - March 23, 2024 Category: Cytology Authors: Mathieu E Rebeaud Satyam Tiwari Bruno Fauvet Adela ïde Mohr Paolo De Los Rios Pierre Goloubinoff Source Type: research
Autorepression of Yeast Hsp70 co-chaperones by intramolecular interactions involving their J-domains
Cell Stress Chaperones. 2024 Mar 21:S1355-8145(24)00060-9. doi: 10.1016/j.cstres.2024.03.008. Online ahead of print.ABSTRACTThe Hsp70 chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) co-evolved with Hsp70s to trigger ATP-hydrolysis and catalytically upload various substrate polypeptides in need to be structurally modified by the chaperone. Here, we measured the protein disaggregation and refolding activities of the main yeast cytosolic Hsp70, Ssa1, in the presence of its most abundant JDPs, Sis1 and Ydj1, and two swap mutants, in which the J-domains have been inte...
Source: Cell Stress and Chaperones - March 23, 2024 Category: Cytology Authors: Mathieu E Rebeaud Satyam Tiwari Bruno Fauvet Adela ïde Mohr Paolo De Los Rios Pierre Goloubinoff Source Type: research
Autorepression of Yeast Hsp70 co-chaperones by intramolecular interactions involving their J-domains
Cell Stress Chaperones. 2024 Mar 21:S1355-8145(24)00060-9. doi: 10.1016/j.cstres.2024.03.008. Online ahead of print.ABSTRACTThe Hsp70 chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) co-evolved with Hsp70s to trigger ATP-hydrolysis and catalytically upload various substrate polypeptides in need to be structurally modified by the chaperone. Here, we measured the protein disaggregation and refolding activities of the main yeast cytosolic Hsp70, Ssa1, in the presence of its most abundant JDPs, Sis1 and Ydj1, and two swap mutants, in which the J-domains have been inte...
Source: Cell Stress and Chaperones - March 23, 2024 Category: Cytology Authors: Mathieu E Rebeaud Satyam Tiwari Bruno Fauvet Adela ïde Mohr Paolo De Los Rios Pierre Goloubinoff Source Type: research
Plasmodium falciparum heat shock proteins as anti-malarial drug targets: An update
Cell Stress Chaperones. 2024 Mar 20:S1355-8145(24)00059-2. doi: 10.1016/j.cstres.2024.03.007. Online ahead of print.ABSTRACTGlobal efforts to eradicate malaria are threatened by multiple factors, particularly the emergence of anti-malarial drug resistant strains of Plasmodium falciparum. Heat shock proteins (HSPs), particularly P. falciparum HSPs (PfHSPs), represent promising drug targets due to their essential roles in parasite survival and virulence across the various life cycle stages. Despite structural similarities between human and malarial HSPs posing challenges, there is substantial evidence for subtle differences ...
Source: Cell Stress and Chaperones - March 22, 2024 Category: Cytology Authors: Tanveer Ahmad Bushra A Alhammadi Shaikha Y Almaazmi Sahar Arafa Gregory L Blatch Tanima Dutta Jason E Gestwicki Robert A Keyzers Addmore Shonhai Harpreet Singh Source Type: research
HSPA9/mortalin inhibition disrupts erythroid maturation through a TP53-dependent mechanism in human CD34+ hematopoietic progenitor cells
In this study, we explored the role of HSPA9 in regulating erythroid maturation using human CD34+ cells. We inhibited the expression of HSPA9 using gene knockdown and pharmacological inhibition, and found that inhibition of HSPA9 disrupted erythroid maturation as well as increased expression of p53 in CD34+ cells. To test whether the molecular mechanism of HSPA9 regulating erythroid maturation is TP53-dependent, we knocked-down HSPA9 and TP53 individually or in combination in human CD34+ cells. We found that knock-down of TP53 partially rescued the erythroid maturation defect induced by HSPA9 knock-down, suggesting that th...
Source: Cell Stress and Chaperones - March 20, 2024 Category: Cytology Authors: Christopher Butler Morgan Dunmire Jaebok Choi Gabor Szalai Anissa Johnson Wei Lei Xin Chen Liang Liu Wei Li Matthew J Walter Tuoen Liu Source Type: research
HSPA9/mortalin inhibition disrupts erythroid maturation through a TP53-dependent mechanism in human CD34+ hematopoietic progenitor cells
In this study, we explored the role of HSPA9 in regulating erythroid maturation using human CD34+ cells. We inhibited the expression of HSPA9 using gene knockdown and pharmacological inhibition, and found that inhibition of HSPA9 disrupted erythroid maturation as well as increased expression of p53 in CD34+ cells. To test whether the molecular mechanism of HSPA9 regulating erythroid maturation is TP53-dependent, we knocked-down HSPA9 and TP53 individually or in combination in human CD34+ cells. We found that knock-down of TP53 partially rescued the erythroid maturation defect induced by HSPA9 knock-down, suggesting that th...
Source: Cell Stress and Chaperones - March 20, 2024 Category: Cytology Authors: Christopher Butler Morgan Dunmire Jaebok Choi Gabor Szalai Anissa Johnson Wei Lei Xin Chen Liang Liu Wei Li Matthew J Walter Tuoen Liu Source Type: research
HSPA9/mortalin inhibition disrupts erythroid maturation through a TP53-dependent mechanism in human CD34+ hematopoietic progenitor cells
In this study, we explored the role of HSPA9 in regulating erythroid maturation using human CD34+ cells. We inhibited the expression of HSPA9 using gene knockdown and pharmacological inhibition, and found that inhibition of HSPA9 disrupted erythroid maturation as well as increased expression of p53 in CD34+ cells. To test whether the molecular mechanism of HSPA9 regulating erythroid maturation is TP53-dependent, we knocked-down HSPA9 and TP53 individually or in combination in human CD34+ cells. We found that knock-down of TP53 partially rescued the erythroid maturation defect induced by HSPA9 knock-down, suggesting that th...
Source: Cell Stress and Chaperones - March 20, 2024 Category: Cytology Authors: Christopher Butler Morgan Dunmire Jaebok Choi Gabor Szalai Anissa Johnson Wei Lei Xin Chen Liang Liu Wei Li Matthew J Walter Tuoen Liu Source Type: research
