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1. Stress biology: Complexity and multifariousness in health and disease.

Author

Mayer, Matthias, Blair, Laura, Blatch, Gregory, Borges, Thiago, Chadli, Ahmed, Chiosis, Gabriela, de Thonel, Aurélie, Dinkova-Kostova, Albena, Ecroyd, Heath, Edkins, Adrienne, Eguchi, Takanori, Fleshner, Monika, Foley, Kevin, Fragkostefanakis, Sotirios, Gestwicki, Jason, Goloubinoff, Pierre, Heritz, Jennifer, Heske, Christine, Hibshman, Jonathan, Joutsen, Jenny, Li, Wei, Lynes, Michael, Mendillo, Marc, Mivechi, Nahid, Mokoena, Fortunate, Okusha, Yuka, Prahlad, Veena, Repasky, Elizabeth, Sannino, Sara, Scalia, Federica, Shalgi, Reut, Sistonen, Lea, Sontag, Emily, van Oosten-Hawle, Patricija, Vihervaara, Anniina, Wickramaratne, Anushka, Wang, Shawn, and Zininga, Tawanda

Subjects
Heat shock proteins, Heat shock response, Heat shock transcription factors, Molecular chaperones, Protein folding diseases, Stress response, Heat-Shock Proteins, Molecular Chaperones, Heat-Shock Response, Medicine, Biology
Abstract

Preserving and regulating cellular homeostasis in the light of changing environmental conditions or developmental processes is of pivotal importance for single cellular and multicellular organisms alike. To counteract an imbalance in cellular homeostasis transcriptional programs evolved, called the heat shock response, unfolded protein response, and integrated stress response, that act cell-autonomously in most cells but in multicellular organisms are subjected to cell-nonautonomous regulation. These transcriptional programs downregulate the expression of most genes but increase the expression of heat shock genes, including genes encoding molecular chaperones and proteases, proteins involved in the repair of stress-induced damage to macromolecules and cellular structures. Sixty-one years after the discovery of the heat shock response by Ferruccio Ritossa, many aspects of stress biology are still enigmatic. Recent progress in the understanding of stress responses and molecular chaperones was reported at the 12th International Symposium on Heat Shock Proteins in Biology, Medicine and the Environment in the Old Town Alexandria, VA, USA from 28th to 31st of October 2023.

Published
2024

3. Author Correction: CBP-HSF2 structural and functional interplay in Rubinstein-Taybi neurodevelopmental disorder

Author

de Thonel, Aurélie, Ahlskog, Johanna K., Daupin, Kevin, Dubreuil, Véronique, Berthelet, Jérémy, Chaput, Carole, Pires, Geoffrey, Leonetti, Camille, Abane, Ryma, Barris, Lluís Cordón, Leray, Isabelle, Aalto, Anna L., Naceri, Sarah, Cordonnier, Marine, Benasolo, Carène, Sanial, Matthieu, Duchateau, Agathe, Vihervaara, Anniina, Puustinen, Mikael C., Miozzo, Federico, Fergelot, Patricia, Lebigot, Élise, Verloes, Alain, Gressens, Pierre, Lacombe, Didier, Gobbo, Jessica, Garrido, Carmen, Westerheide, Sandy D., David, Laurent, Petitjean, Michel, Taboureau, Olivier, Rodrigues-Lima, Fernando, Passemard, Sandrine, Sabéran-Djoneidi, Délara, Nguyen, Laurent, Lancaster, Madeline, Sistonen, Lea, and Mezger, Valérie

Published
2023
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4. Second Virtual International Symposium on Cellular and Organismal Stress Responses, September 8–9, 2022

Author

van Oosten-Hawle, Patricija, Backe, Sarah J., Ben-Zvi, Anat, Bourboulia, Dimitra, Brancaccio, Mara, Brodsky, Jeff, Clark, Melody, Colombo, Giorgio, Cox, Marc B., De Los Rios, Paolo, Echtenkamp, Frank, Edkins, Adrienne, Freeman, Brian, Goloubinoff, Pierre, Houry, Walid, Johnson, Jill, LaPointe, Paul, Li, Wei, Mezger, Valerie, Neckers, Len, Nillegoda, Nadinath B., Prahlad, Veena, Reitzel, Adam, Scherz-Shouval, Ruth, Sistonen, Lea, Tsai, Francis T. F., Woodford, Mark R., Mollapour, Mehdi, and Truman, Andrew W.

Published
2023

6. CBP-HSF2 structural and functional interplay in Rubinstein-Taybi neurodevelopmental disorder

Author

de Thonel, Aurélie, Ahlskog, Johanna K., Daupin, Kevin, Dubreuil, Véronique, Berthelet, Jérémy, Chaput, Carole, Pires, Geoffrey, Leonetti, Camille, Abane, Ryma, Barris, Lluís Cordón, Leray, Isabelle, Aalto, Anna L., Naceri, Sarah, Cordonnier, Marine, Benasolo, Carène, Sanial, Matthieu, Duchateau, Agathe, Vihervaara, Anniina, Puustinen, Mikael C., Miozzo, Federico, Fergelot, Patricia, Lebigot, Élise, Verloes, Alain, Gressens, Pierre, Lacombe, Didier, Gobbo, Jessica, Garrido, Carmen, Westerheide, Sandy D., David, Laurent, Petitjean, Michel, Taboureau, Olivier, Rodrigues-Lima, Fernando, Passemard, Sandrine, Sabéran-Djoneidi, Délara, Nguyen, Laurent, Lancaster, Madeline, Sistonen, Lea, and Mezger, Valérie

Published
2022
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7. Proteomic profiling identifies a direct interaction between heat shock transcription factor 2 and the focal adhesion adapter talin‐1.

Author

Da Silva, Alejandro J., Hästbacka, Hendrik S. E., Luoto, Jens C., Gough, Rosemarie E., Coelho‐Rato, Leila S., Laitala, Leena M., Goult, Benjamin T., Imanishi, Susumu Y., Sistonen, Lea, and Henriksson, Eva

Subjects
HEAT shock factors, TRANSCRIPTION factors, FOCAL adhesions, ADAPTOR proteins, SEQUENCE alignment
Abstract

Heat shock factor 2 (HSF2) is a versatile transcription factor that regulates gene expression under stress conditions, during development, and in disease. Despite recent advances in characterizing HSF2‐dependent target genes, little is known about the protein networks associated with this transcription factor. In this study, we performed co‐immunoprecipitation coupled with mass spectrometry analysis to identify the HSF2 interactome in mouse testes, where HSF2 is required for normal sperm development. Endogenous HSF2 was discovered to form a complex with several adhesion‐associated proteins, a finding substantiated by mass spectrometry analysis conducted in human prostate carcinoma PC‐3 cells. Notably, this group of proteins included the focal adhesion adapter protein talin‐1 (TLN1). Through co‐immunoprecipitation and proximity ligation assays, we demonstrate the conservation of the HSF2‐TLN1 interaction from mouse to human. Additionally, employing sequence alignment analyses, we uncovered a TLN1‐binding motif in the HSF2 C terminus that binds directly to multiple regions of TLN1 in vitro. We provide evidence that the 25 C‐terminal amino acids of HSF2, fused to EGFP, are sufficient to establish a protein complex with TLN1 and modify cell–cell adhesion in human cells. Importantly, this TLN1‐binding motif is absent in the C‐terminus of a closely related HSF family member, HSF1, which does not form a complex with TLN1. These results highlight the unique molecular characteristics of HSF2 in comparison to HSF1. Taken together, our data unveil the protein partners associated with HSF2 in a physiologically relevant context and identifies TLN1 as the first adhesion‐related HSF2‐interacting partner. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Second Virtual International Symposium on Cellular and Organismal Stress Responses, September 8–9, 2022 [Meeting Review]

Author

van Oosten-Hawle, Patricija, Backe, Sarah J., Ben-Zvi, Anat, Bourboulia, Dimitra, Brancaccio, Mara, Brodsky, Jeff, Clark, Melody, Colombo, Giorgio, Cox, Marc B., De Los Rios, Paolo, Echtenkamp, Frank, Edkins, Adrienne, Freeman, Brian, Goloubinoff, Pierre, Houry, Walid, Johnson, Jill, LaPointe, Paul, Li, Wei, Mezger, Valerie, Neckers, Len, Nillegoda, Nadinath B., Prahlad, Veena, Reitzel, Adam, Scherz-Shouval, Ruth, Sistonen, Lea, Tsai, Francis T. F., Woodford, Mark R., Mollapour, Mehdi, Truman, Andrew W., van Oosten-Hawle, Patricija, Backe, Sarah J., Ben-Zvi, Anat, Bourboulia, Dimitra, Brancaccio, Mara, Brodsky, Jeff, Clark, Melody, Colombo, Giorgio, Cox, Marc B., De Los Rios, Paolo, Echtenkamp, Frank, Edkins, Adrienne, Freeman, Brian, Goloubinoff, Pierre, Houry, Walid, Johnson, Jill, LaPointe, Paul, Li, Wei, Mezger, Valerie, Neckers, Len, Nillegoda, Nadinath B., Prahlad, Veena, Reitzel, Adam, Scherz-Shouval, Ruth, Sistonen, Lea, Tsai, Francis T. F., Woodford, Mark R., Mollapour, Mehdi, and Truman, Andrew W.

Abstract

The Second International Symposium on Cellular and Organismal Stress Responses took place virtually on September 8–9, 2022. This meeting was supported by the Cell Stress Society International (CSSI) and organized by Patricija Van Oosten-Hawle and Andrew Truman (University of North Carolina at Charlotte, USA) and Mehdi Mollapour (SUNY Upstate Medical University, USA). The goal of this symposium was to continue the theme from the initial meeting in 2020 by providing a platform for established researchers, new investigators, postdoctoral fellows, and students to present and exchange ideas on various topics on cellular stress and chaperones. We will summarize the highlights of the meeting here and recognize those that received recognition from the CSSI.

Published
2023

31. Interplay between mammalian heat shock factors 1 and 2 in physiology and pathology.

Author

Roos‐Mattjus, Pia and Sistonen, Lea

Subjects
*HEAT shock factors, *PHYSIOLOGY, *TRANSCRIPTION factors, *PROTHROMBIN, *DISEASE progression, *POST-translational modification
Abstract

The heat‐shock factors (HSFs) belong to an evolutionary conserved family of transcription factors that were discovered already over 30 years ago. The HSFs have been shown to a have a broad repertoire of target genes, and they also have crucial functions during normal development. Importantly, HSFs have been linked to several disease states, such as neurodegenerative disorders and cancer, highlighting their importance in physiology and pathology. However, it is still unclear how HSFs are regulated and how they choose their specific target genes under different conditions. Posttranslational modifications and interplay among the HSF family members have been shown to be key regulatory mechanisms for these transcription factors. In this review, we focus on the mammalian HSF1 and HSF2, including their interplay, and provide an updated overview of the advances in understanding how HSFs are regulated and how they function in multiple processes of development, aging, and disease. We also discuss HSFs as therapeutic targets, especially the recently reported HSF1 inhibitors. [ABSTRACT FROM AUTHOR]

Published
2022
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43. Stress-induced transcriptional memory accelerates promoter-proximal pause release and decelerates termination over mitotic divisions

Author

Vihervaara, Anniina, Mahat, Dig Bijay, Himanen, Samu, V, Blom, Malin A. H., Lis, John T., Sistonen, Lea, Vihervaara, Anniina, Mahat, Dig Bijay, Himanen, Samu, V, Blom, Malin A. H., Lis, John T., and Sistonen, Lea

Abstract

Heat shock instantly reprograms transcription. Whether gene and enhancer transcription fully recover from stress and whether stress establishes a memory by provoking transcription regulation that persists through mitosis remained unknown. Here, we measured nascent transcription and chromatin accessibility in unconditioned cells and in the daughters of stress-exposed cells. Tracking transcription genome-wide at nucleotide-resolution revealed that cells precisely restored RNA polymerase II (Pol II) distribution at gene bodies and enhancers upon recovery from stress. However, a single heat exposure in embryonic fibroblasts primed a faster gene induction in their daughter cells by increasing promoter-proximal Pol II pausing and by accelerating the pause release. In K562 erythroleukemia cells, repeated stress refined basal and heat-induced transcription over mitotic division and decelerated termination-coupled pre-mRNA processing. The slower termination retained transcripts on the chromatin and reduced recycling of Pol II. These results demonstrate that heat-induced transcriptional memory acts through promoter-proximal pause release and pre-mRNA processing at transcription termination., QC 20210601

Published
2021
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46. The 2021 FASEB Virtual Catalyst Conference on Extracellular and Organismal Proteostasis in Health and Disease, February 3‐4, 2021

Author

Lior, Chen, primary, Hodge, Francesca, additional, De‐Souza, Evandro A., additional, Bourboulia, Dimitra, additional, Calderwood, Stuart K., additional, David, Della, additional, Allan Drummond, D., additional, Edkins, Adrienne, additional, Morimoto, Richard I., additional, Prahlad, Veena, additional, Rechavi, Oded, additional, Sistonen, Lea, additional, Wilson, Mark, additional, Wiseman, R. Luke, additional, Zanetti, Maurizio, additional, Taylor, Rebecca, additional, Scherz‐Shouval, Ruth, additional, and Oosten‐Hawle, Patricija, additional

Published
2021
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48. Increased HSF1 expression predicts shorter disease-specific survival of prostate cancer patients following radical prostatectomy

Author

Björk, Johanna K., Ahonen, Ilmari, Mirtti, Tuomas, Erickson, Andrew, Rannikko, Antti, Butzow, Anna, Nordling, Stig, Lundin, Johan, Lundin, Mikael, Sistonen, Lea, Nees, Matthias, Akerfelt, Malin, Doctoral Programme in Clinical Research, University Management, Institute for Molecular Medicine Finland, Department of Pathology, Medicum, Urologian yksikkö, Department of Surgery, Doctoral Programme in Biomedicine, Johan Edvard Lundin / Principal Investigator, and HUS Abdominal Center

Subjects
3122 Cancers, fungi, biomarker heat shock factor predictive marker prostate cancer tissue microarray (TMA) interest, biomarker, tissue microarray (TMA), heat shock factor, prostate cancer, predictive marker, Research Paper
Abstract

Bjork, Johanna K Ahonen, Ilmari Mirtti, Tuomas Erickson, Andrew Rannikko, Antti Butzow, Anna Nordling, Stig Lundin, Johan Lundin, Mikael Sistonen, Lea Nees, Matthias Akerfelt, Malin eng Oncotarget. 2018 Jul 27;9(58):31200-31213. doi: 10.18632/oncotarget.25756. eCollection 2018 Jul 27. Prostate cancer is a highly heterogeneous disease and the clinical outcome is varying. While current prognostic tools are regarded insufficient, there is a critical need for markers that would aid prognostication and patient risk-stratification. Heat shock transcription factor 1 (HSF1) is crucial for cellular homeostasis, but also a driver of oncogenesis. The clinical relevance of HSF1 in prostate cancer is, however, unknown. Here, we identified HSF1 as a potential biomarker in mRNA expression datasets on prostate cancer. Clinical validation was performed on tissue microarrays from independent cohorts: one constructed from radical prostatectomies from 478 patients with long term follow-up, and another comprising of regionally advanced to distant metastatic samples. Associations with clinical variables and disease outcomes were investigated. Increased nuclear HSF1 expression correlated with disease advancement and aggressiveness and was, independently from established clinicopathological variables, predictive of both early initiation of secondary therapy and poor disease-specific survival. In a joint model with the clinical Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score, nuclear HSF1 remained a predictive factor of shortened disease-specific survival. The results suggest that nuclear HSF1 expression could serve as a novel prognostic marker for patient risk-stratification on disease progression and survival after radical prostatectomy.

Published
2018

49. Role of heat-shock factor 2 in cerebral cortex formation and as a regulator of p35 expression

Author

Yunhua Chang, Ostling, Paivi, Akerfelt, Malin, Trouillet, Diane, Rallu, Murielle, Gitton, Yorick, Fatimy, Rachid El, Fardeau, Vivienne, Le Crom, Stephen, Morange, Michel; Sistonen, Lea, and Mezger, Valerie

Subjects
Heat shock proteins -- Research, Genetic regulation -- Research, Genetic research, Biological sciences
Abstract

The role of heat-shock factor 2 in cerebral cortex displays mispositioning of neurons of superficial layers. The heat-shock factor 2 affects cellular populations that assist in radial migration and directly regulates the expression of p35, a crucial actor of radial neuronal migration.

Published
2006

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