4.3 Review

Second Virtual International Symposium on Cellular and Organismal Stress Responses, September 8-9, 2022

Related references

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Article Biochemistry & Molecular Biology

A fluorescent multi-domain protein reveals the unfolding mechanism of Hsp70

Satyam Tiwari et al.

Summary: The lack of comprehensive characterization of heterogeneous protein aggregates has hindered the detailed understanding of how Hsp70 chaperones protect cells against aggregation. In this study, a reporter chaperone substrate called MLucV was designed, which formed discrete small aggregates upon denaturation. Utilizing Forster resonance energy transfer and enzymatic activity measurements, unprecedented details about the aggregated, unfolded, Hsp70-bound, and native conformations of MLucV were obtained. The results reveal that Hsp70 first facilitates ATP-fueled disaggregation and unfolding of the pre-aggregated substrate, stretching MLucV beyond unfolded conformations, followed by native refolding.

NATURE CHEMICAL BIOLOGY (2023)

Editorial Material Cell Biology

Chaperone networks are shaped by cellular differentiation and identity

Khairun Nisaa et al.

Summary: Chaperone expression is regulated during development to establish tissue-specific networks. However, the molecular mechanisms behind this specificity are mostly unknown. Recent evidence suggests that differentiation transcription factors play a role in rewiring the chaperone network to meet the folding demands of the proteome, which has implications for the manifestation of protein misfolding diseases in specific tissues.

TRENDS IN CELL BIOLOGY (2022)

Article Medicine, Research & Experimental

The molecular chaperone GRP170 protects against ER stress and acute kidney injury in mice

Aidan W. Porter et al.

Summary: Molecular chaperones, such as GRP170, play a crucial role in maintaining cellular homeostasis and kidney physiology. Deficiency of GRP170 causes hypovolemia, hyperaldosteronemia, ion homeostasis dysregulation, loss of epithelial sodium channel (ENaC), and exhibits signs of acute kidney injury. Furthermore, GRP170 deficiency activates the unfolded protein response (UPR), which is also seen in various other causes of acute kidney injury.

JCI INSIGHT (2022)

Review Biochemistry & Molecular Biology

The role of cellular proteostasis in antitumor immunity

Rebecca Mercier et al.

Summary: Immune checkpoint blockade therapy is a significant advancement in cancer treatment. Proteostasis plays a crucial role in maintaining cellular function and regulating gene expression changes. This review focuses on the role of proteostasis in regulating immune responses and determining the immunogenicity of cancer cells.

JOURNAL OF BIOLOGICAL CHEMISTRY (2022)

Article Biochemistry & Molecular Biology

Assembly principles of the human R2TP chaperone complex reveal the presence of R2T and R2P complexes

Thiago Seraphim et al.

Summary: The R2TP complex, formed by RUVBL1 and RUVBL2 ATPases, associates with PIH1D1 and RPAP3 proteins and plays a role in promoting the formation of macromolecular complexes. RPAP3 is identified as the central subunit of R2TP, linking PIH1D1 and RUVBL1/2. The study provides insights into the structure and function of the R2TP complex.

STRUCTURE (2022)

Article Cell Biology

O-GlcNAcylation suppresses TRAP1 activity and promotes mitochondrial respiration

Seungchan Kim et al.

Summary: The study shows that O-GlcNAcylation of TRAP1 decreases its ATPase activity, impacting mitochondrial metabolism, and this modification occurs following mitochondrial import. Furthermore, TRAP1-O-GlcNAcylation regulates mitochondrial metabolism by attenuating its chaperone activity.

CELL STRESS & CHAPERONES (2022)

Article Multidisciplinary Sciences

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

Aurelie de Thonel et al.

Summary: This study reveals the contribution of a stress-responsive pathway to Rubinstein-Taybi syndrome (RSTS), indicating that impaired HSF2 acetylation due to RSTS-associated CBP/EP300 mutations alters the expression of neurodevelopmental players, leading to cell-cell adhesion defects.

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Article Biochemistry & Molecular Biology

HSFs drive transcription of distinct genes and enhancers during oxidative stress and heat shock

Samu Himanen et al.

Summary: This study investigated how heat shock factors HSF1 and HSF2 coordinate transcription of genes and enhancers during oxidative stress and heat shock. The researchers found that the release of paused RNA polymerase II is a common mechanism regulating gene transcription, while enhancers are activated through the recruitment of Pol II. HSF1 and HSF2 also function as stress-responsive factors that activate specific genes and enhancers in a stress type-specific manner. HSF1 activates chaperone genes specifically in heat-shocked cells, while it trans-activates oxidative stress-specific genes upon oxidative stress.

NUCLEIC ACIDS RESEARCH (2022)

Review Biochemistry & Molecular Biology

The Role of Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization

Jeffrey Lynham et al.

Summary: Hsp90 is a ubiquitous molecular chaperone that plays an important role in cell signaling pathways. Its interactions with specific chaperones and cochaperones determine the folding of client proteins. Although it has multiple roles in protein complex assembly, the detailed mechanisms are still not fully understood.

BIOMOLECULES (2022)

Article Biochemistry & Molecular Biology

Comprehensive characterization of the Hsp70 interactome reveals novel client proteins and interactions mediated by posttranslational modifications

Nitika et al.

Summary: The novel use of cross-linking mass spectrometry (XL-MS) has led to a comprehensive characterization of the Hsp70 protein interactome in yeast, providing new insights into its function and posttranslational modifications (PTMs). This study highlights the importance of PTMs in regulating client protein function through facilitating interactions with chaperones.

PLOS BIOLOGY (2022)

Review Biochemistry & Molecular Biology

HSP90 as a regulator of extracellular matrix dynamics

Abir Chakraborty et al.

Summary: The extracellular matrix (ECM) is vital for maintaining tissue homeostasis by providing cellular cues, and imbalance in ECM production and turnover can lead to diseases. Hsp90 plays a central role in regulating protein homeostasis, including in the ECM, and changes in its levels or activity can contribute to ECM-related diseases. Prognostic value of Hsp90 levels and potential therapeutic benefits of its inhibition in conditions associated with ECM dysfunction are being explored.

BIOCHEMICAL SOCIETY TRANSACTIONS (2021)

Review Cell Biology

Extracellular HSP90 Machineries Build Tumor Microenvironment and Boost Cancer Progression

Pietro Poggio et al.

Summary: Extracellular HSP90 complexes released by cancer cells in the tumor microenvironment play essential roles in tumor growth and progression, highlighting their potential as targets for innovative diagnostic tools and therapies.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Resilience in Greenland intertidal Mytilus: The hidden stress defense

Melody S. Clark et al.

Summary: The Arctic is warming rapidly, allowing invasive species to survive. Some marine species can tolerate high temperatures, but the Mytilus edulis is usually unable to survive in extreme heat. Research indicates that M. edulis has a wide acclimation ability, enabling it to withstand Arctic warming and temperature variations.

SCIENCE OF THE TOTAL ENVIRONMENT (2021)

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The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones

Netta Shemesh et al.

Summary: The authors demonstrate that the human chaperone system consists of ubiquitous core chaperones and tissue-specific variable chaperones, and perturbation of which leads to tissue-specific phenotypes. The core chaperones are significantly more abundant across tissues and important for cell survival, forming tissue-specific functional networks. This functional organization is established in development and declines with age, highlighting the importance of understanding tissue-specific differences in protein folding capacities.

NATURE COMMUNICATIONS (2021)

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Targeting the Extracellular HSP90 Co-Chaperone Morgana Inhibits Cancer Cell Migration and Promotes Anticancer Immunity

Laura Secli et al.

Summary: This study found that the HSP90 co-chaperone Morgana is released by cancer cells and induces cancer cell migration through TLR2, TLR4, and LRP1. Targeting Morgana extracellular activity may inhibit metastasis and enhance the CD8(+) T-cell-mediated antitumor immune response, suggesting therapeutic value in cancer treatment.

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Design of Disruptors of the Hsp90-Cdc37 Interface

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Post-translational modifications of Hsp70 family proteins: Expanding the chaperone code

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Post-translational modifications of Hsp90 and translating the chaperone code

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Synthesis and evaluation of esterified Hsp70 agonists in cellular models of protein aggregation and folding

Annette N. Chiang et al.

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The FKBP52 Cochaperone Acts in Synergy with β-Catenin to Potentiate Androgen Receptor Signaling

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Morgana and Melusin Two fairies chaperoning signal transduction

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