Search Results (649)

Small heat shock proteins (Hsp20s) function as essential molecular chaperones in plant stress responses, yet their genome-wide characterization in sunflower (Helianthus annuus L.) remains lacking and their functional role in heat response is also unknown. In this study, 65 HaHsp20 genes were identified in sunflower through a comprehensive genome-wide analysis based on the conserved ACD (α-crystallin) domain. The expansion of this family was primarily driven by whole-genome duplication (WGD) or segmental duplication events, with the CI subfamily (20 members) representing the most significantly expanded lineage-specific clade. While all HaHsp20 proteins harbor the conserved α-crystallin domain (ACD), they exhibit diverse molecular weights (11.31–53.35 kDa), isoelectric points (4.71–9.75), and subcellular localization patterns. Promoter cis-regulatory element analysis revealed a predominance of ABA and MeJA-responsive elements but only two canonical heat shock elements. Transcriptome and RT-qPCR analyses revealed that most HaHsp20 genes are responsive to heat stress, with seven HaHsp20 genes exhibiting extremely upregulated expression (more than 1000-fold) after 10 h of 45 °C treatment. Among these, HaHsp21.59 and HaHsp25.91 showed an increase of over 4000-fold in expression. These findings provide a comprehensive foundation for understanding the evolutionary history and expression dynamics of the HaHsp20 family in sunflower, and highlight HaHsp21.59 and HaHsp25.91 as promising candidate genes for future functional validation of their potential roles in heat stress tolerance. Full article

As the core molecular chaperones of the cellular stress response, the heat shock protein (HSP) family has gained extensive attention for its role in the occurrence, development, and target organ damage of hypertension. This review aimed to comprehensively summarize the research progress of the HSP family in the field of hypertension, and to analyze its key roles in the pathogenesis of hypertension, including its regulatory effects on key pathological processes such as endothelial dysfunction, proliferation and migration of vascular smooth muscle cells, oxidative stress, and inflammatory responses. It also summarized the potential value of HSPs as biomarkers in the early diagnosis, condition monitoring, and prognostic evaluation of hypertension. Moreover, it discussed in depth the efficacy and safety of intervention strategies targeting HSPs, including the regulation of HSPs by gene editing, the targeted effects of small-molecule inhibitors, and the modulatory effects of natural products. We need to strengthen interdisciplinary collaboration mechanisms, accelerate the transformation of basic research results into clinical applications, carry out large-scale clinical trials, and develop specific modulators in the future, so as to ultimately provide solid scientific theoretical support and a practical clinical basis for the precise prevention and treatment of hypertension. The findings of this review not only provide novel insights into the pathogenesis of hypertension but also lay a theoretical foundation for the development of HSP-based biomarkers and targeted therapeutic strategies. Full article

Heat stress severely constrains wheat productivity, yet the mechanisms underlying thermotolerance remain incompletely understood. This study integrated physiological, biochemical, molecular, and ultrastructural analyses to characterize heat-stress responses in four bread wheat (Triticum aestivum L.) genotypes contrasting in heat tolerance. Membrane injury was assessed by membrane damage rate, lipid peroxidation by malondialdehyde accumulation, antioxidant defense by SOD, CAT, GPX, and BPX activities, and stress-responsive regulation by qRT-PCR analysis of DREB, HSP16.9, and SOD isoforms. HSP16.9 protein accumulation was further evaluated by Western blotting. Heat stress increased membrane damage and MDA accumulation in all genotypes; however, tolerant Murov 2 and Zirva 85 showed lower oxidative membrane injury than sensitive Aran and Gyzyl bugda. Thermotolerance was associated with stronger antioxidant activation, enhanced DREB and HSP16.9 induction, and more coordinated FeSOD and MnSOD expression. The HSP16.9 protein accumulated after heat treatment, supporting its role as a stress-responsive molecular chaperone. Separate correlation analyses of tolerant and sensitive genotypes revealed stronger coordination among transcriptional, chaperone-related, and antioxidant markers in tolerant genotypes, whereas sensitive genotypes showed a more fragmented response. Microscopy further showed better preservation of chloroplast, mitochondrial, and mesophyll organization in the tolerant genotype relative to the sensitive counterpart, indicating integrated cellular protection. Together, these responses define a coordinated tolerance strategy that may guide the selection of heat-resilient wheat genotypes. Full article

The plastid stroma-localized chaperone HSP90C is essential for maintaining chloroplast proteostasis and facilitating protein translocation. Prior research has established HSP90C’s imperative role in the SEC translocase-dependent transport of the photosystem II subunit PsbO1 and its interaction with the SEC1 translocase motor protein SecA1. However, the exact mechanism of this interaction remains to be explored. In this study, we delineated the interactional mode of HSP90C and SecA1 with the model client protein. Yeast two-hybrid and in vitro ATPase activity analyses with purified proteins revealed PsbO1 may bind to HSP90C at multiple sites, including the DPW motif within the C-terminal extension (CTE) region, suggesting a possible client-loading mechanism unique to plastid orthologs. We also confirmed that glycine-646 is important in mediating substrate interaction, though it conferred a much weaker binding than the CTE region, thereby elucidating a critical role for the amino acid whose mutation resulted in visible plant phenotypes. Our in vitro biochemical assays also demonstrated that the stromal intermediate form of PsbO1 with the thylakoid signal peptide (tSP) significantly enhanced SecA1 ATPase activity, suggesting a preferential binding to the motor protein. On the other hand, the mature domain of the PsbO1, excluding the tSP sequence, inhibited HSP90C ATPase activity. We also observed the HSP90C-PsbO1-SecA1 ternary complex was stabilized by the presence of the client tSP. This work therefore provides new insights into the functional mechanisms of HSP90C and its contribution to chloroplast stromal protein stabilization and thylakoid protein transport. Full article

Protein Phosphatase 5 (PP5) is an evolutionarily conserved serine/threonine phosphatase with a unique tetratricopeptide domain. It has been implicated in a wide range of cellular processes in mammals, but its function in plants is unknown. Here, we uncovered that Arabidopsis PP5 is required for immunity mediated by the nucleotide-binding leucine-rich repeat immune receptor protein SUMM2. Loss-of-function mutations in PP5 suppress the autoimmune phenotypes caused by the activation of SUMM2 due to the disruption of the MEKK1-MKK1/MKK2-MPK4 kinase cascade. Further biochemical analysis revealed that SUMM2 interacts with Heat Shock Protein 90 (HSP90) and PP5, and SUMM2 level is reduced in pp5 knockout mutant plants, suggesting that PP5 promotes the accumulation of SUMM2, likely through its association with the HSP90 chaperone complex. Full article

Heat shock protein 90 (HSP90) is a molecular chaperone essential for maintaining the stability of many oncogenic client proteins. Although several HSP90 inhibitors (HSP90i) have entered clinical trials, their use has been limited by toxicity and resistance, underscoring the need for improved therapeutic strategies. In this study, we assessed the therapeutic potential of a new HSP90i, SP11, in T-cell acute lymphoblastic leukemia (T-ALL) in vitro and in the DLA mouse model in vivo, using single-cell transcriptomic profiling. Single-cell RNA sequencing showed that SP11 treatment reduces key oncogenic drivers, including MYC, BCL2, and stemness-related genes, consistent with impaired leukemic survival programs. In the DLA mouse model, SP11-mediated HSP90 inhibition was associated with alterations in the tumor microenvironment, including increased immune cell representation and enrichment of cytokine- and antigen-presentation-related transcriptional pathways. Despite these antitumor effects, a distinct subpopulation of cells continued to express or re-express MYC and BCL2, suggesting the development of early adaptive resistance. Consistent with these findings, an SP11-resistant MOLT4 cell line maintained high levels of MYC and BCL2 at both the transcript and protein levels, maintained CD44 expression, and exhibited altered inflammatory cytokine signaling. Functional studies confirmed that pharmacological inhibition of BCL2 notably increased SP11 sensitivity, supporting a rational combination strategy. Collectively, our results show that SP11 may exert both tumor-intrinsic and immune-modulating effects and reveal transcriptionally defined adaptive cellular states linked to resistance. This study provides mechanistic in sights into responses to HSP90 inhibition and supports combination approaches for improving therapeutic outcomes in T-ALL. Full article

Heat shock proteins (HSPs) are highly conserved molecular chaperones that play a key role in maintaining protein homeostasis and cellular survival under stress conditions. Clinically relevant human pathogenic fungi include opportunistic fungi, dimorphic fungi, dermatophytes, Mucorales, and other pathogenic groups. HSPs, including Hsp90, Hsp70, Hsp60, Hsp40, and Hsp110, are essential for the correct nascent protein folding, aggregation prevention, and degradation of misfolded polypeptides. Fungal pathogens frequently encounter environmental and host-imposed stresses, including oxidative stress, temperature fluctuations, and antifungal treatments. This review synthesizes and critically analyzes current evidence on the role of HSP families in essential processes linked to fungal virulence, including morphogenetic transitions, biofilm formation, maintenance of cell wall integrity, and interactions with host immune cells. Beyond their canonical chaperone functions, HSPs act as central mediators in pathogenic processes, such as morphogenesis transitions, biofilm formation, cell wall integrity, and interactions with host immune cells. Hsp90 stabilizes key signaling proteins involved in stress responses, morphogenesis, and antifungal resistance, while Hsp60 and Hsp70 contribute to mitochondrial function, cell wall integrity, and immune modulation. Disruption of these chaperones impairs growth, reduces virulence, and increases susceptibility to antifungal agents. The rise of antifungal resistance underscores the urgent need for new therapeutic strategies. Targeting fungal HSPs has emerged as a promising approach due to their essential roles in stress tolerance and pathogenesis. Hsp90 inhibitors, including geldanamycin derivatives and other small molecules, have demonstrated the ability to impair fungal growth, reduce virulence traits, and sensitize resistant strains to conventional antifungal drugs. Combining HSP inhibitors with existing antifungal drugs represents a potential strategy to overcome resistance and improve treatment outcomes. This review summarizes the current knowledge on HSPs in pathogenic fungi, focusing on their roles in stress adaptation, virulence, host-pathogen interaction, antifungal resistance, and their potential as targets for novel antifungal therapies. Full article

During development, stem cells rapidly proliferate and differentiate to form the embryo and the placenta, requiring intensive increases in cellular protein synthesis and changes to the cell architecture. Chaperone proteins, including the small heat shock proteins (HSPs), are critical assistants to protein folding, preventing protein aggregation, and promoting autophagy. Mitogen-activated protein kinase kinase kinase 4 (MAP3K4) is a stress-activated kinase that promotes fetal and placental growth. MAP3K4 directly activates p38 and JNK in trophoblast stem (TS) cells by phosphorylating MAP2K3 and MAP2K4/7, respectively. In addition, MAP3K4 promotes activation of the Akt signaling pathway by controlling Igf1r expression. TS cells differentiate to placental trophoblasts comprising the junctional zone (JZ) and labyrinth (LAB) placental layers. In this study, we demonstrate that JZ differentiation transiently increases JNK activity, whereas LAB differentiation induces sustained p38, JNK, and Akt activation. Each of these pathways is inhibited in MAP3K4 kinase-inactive (KI) LAB^KI trophoblasts. JZ and LAB differentiation also induces HSP22 and HSP27 expression and HSP27 phosphorylation; these are also reduced in TS^KI and LAB^KI cells. JZ and LAB differentiation induces GABARAP-positive autophagosomes that are deficient in KI cells. Altogether, our findings demonstrate that MAP3K4 is critical for responses during differentiation in placental trophoblasts. Full article

Cold stress poses a significant challenge to aquatic organisms, affecting their survival, growth, and metabolic processes. This review explores the molecular mechanisms by which fish, crustaceans, and mollusks respond to cold stress, highlighting the shared and species-specific pathways that facilitate adaptation. Common responses to cold stress include modulation of energy metabolism, regulation of oxidative stress, immune responses, and maintenance of proteostasis. In particular, the activation of the adenosine 5′-monophosphate-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) pathways plays a critical role in regulating energy balance and autophagy in response to low temperatures. Furthermore, we examine the specific adaptive mechanisms employed by different groups of aquatic organisms. Fish utilize pathways such as peroxisome proliferator-activated receptor alpha/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPAR/PGC-1α) and fatty acid oxidation to optimize energy utilization and improve cold tolerance. Crustaceans rely on crustacean hyperglycemic hormone (CHH) signaling and AMPK pathway activation, while mollusks employ metabolic suppression and glycogen storage to survive cold exposure. Moreover, the regulation of autophagy and apoptosis, mediated by p53 and cyclin-dependent kinase 1 (Cdk1), ensures the survival of healthy cells under prolonged cold stress, with autophagy maintaining energy homeostasis and apoptosis eliminating damaged cells. This review also discusses the role of molecular chaperones like heat shock protein 70 (HSP70) and the ubiquitin-proteasome system (UPS) in protein homeostasis, highlighting their importance to protect cells under cold stress. The combined action of these molecular pathways allows aquatic organisms to cope with and adapt to cold environments, ensuring cellular integrity and enhancing survival. Future research should focus on integrating molecular, physiological, and ecological approaches to better understand cold tolerance mechanisms and improve aquaculture practices under climate change scenarios. Full article

Background: Heat shock protein 100 (HSP100) is a key molecular chaperone that maintains intracellular proteostasis and enhances plant tolerance. However, the HSP100 gene family in soybean (Glycine max) has not been systematically characterized. Methods: In this study, we performed genome-wide identification and comprehensive analysis of the GmHSP100 gene family and analyzed their phylogeny, genomic distribution, synteny, protein structures, subcellular localization, promoter cis-elements, and expression patterns under heat and salt stresses via bioinformatics approaches and quantitative real-time PCR (qRT-PCR) validation. Results: Thirteen GmHSP100 members were identified, which were classified into CLPB, CLPC and CLPD subfamilies. Segmental and whole-genome duplications primarily drove the expansion of this gene family. All encoded proteins possessed conserved AAA+ ATPase domains, with distinct motifs across subfamilies. Most proteins localized to the cytoplasm, while CLPC and CLPD targeted chloroplasts and GmCLPB4 localized to mitochondria. Promoter analysis identified numerous elements associated with light, hormone and stress responses. Expression profiling showed strong tissue specificity and time-dependent stress-treatment induction. Heat stress triggered rapid and strong upregulation of the GmHSP100s, whereas salt stress salt stress induced their relatively delayed and sustained expression. Conclusions: These findings reveal the evolutionary conservation and diversification of the GmHSP100 gene family in soybean, providing a foundational framework for understanding the functions of GmHSP100 in stress adaptation. Full article

Unexplained infertility affects up to 30% of couples and has been associated with heat shock proteins (HSP) and endometrial stress. HSPs and their co-chaperones are part of a complex network of proteins responsible for maintaining protein homeostasis and cell survival. This exploratory hypothesis-generating study investigated the possible relationship between HSPs and unexplained infertility. Twenty-five women were recruited from an IVF clinic. Eleven were confirmed for unexplained infertility (UI), while fourteen were age- and body mass index (BMI)-matched couples with confirmed male factor infertility (MFI), acting as controls. Blood samples were obtained at day 21 of the luteal phase, and plasma measurement of 19 HSPs and co-chaperones undertaken using the slow off-rate modified aptamer (SomaScan) platform. Welch’s t-test and a permutation test were used to compare group means, and Pearson’s correlations to examine relationships with HSPs. Of the 19 proteins measured, plasma HSP70 was decreased (permutation p = 0.002) in cases with unexplained infertility, while HSC70 and STIP1 were increased (permutation p = 0.017 and p = 0.001, respectively) when compared to MFI control. HSP70 was negatively correlated to both HSC70 and STIP 1 in UI (r = −0.77, permutation p = 0.017; −0.80, permutation p = 0.003, respectively), but not in MFI, whilst HSC70 and STIP1 were positively correlated in both UI and MFI (r = 0.93, permutation p = 0.001; r = 0.65, permutation p = 0.035, respectively). The HSP70-HSC70-STIP1 axis showed HSC70-STIP1 coupling with an inverse relationship with inducible HSP70, findings that may suggest dysregulation of constitutive and stress-inducible chaperone systems in UI. Full article

Introduction: Heat shock proteins (HSPs) are stress-responsive molecular chaperones that are frequently dysregulated in cancer and contribute to tumorigenesis, invasion, metastasis, immune interactions, and resistance to therapy. Distinct HSP families, including HSP27, HSP60, HSP70, HSP90, and HSP110, promote malignant progression through complementary effects on apoptosis regulation, mitochondrial function, proteostasis, and stabilization of oncogenic signaling pathways. This makes HSPs attractive therapeutic targets. Their coordinated roles within stress-adaptive chaperone networks further garner interest in targeting multiple HSP families in cancer therapy. Discussion: Preclinical and clinical studies have established multiple HSP families as promising anticancer targets; however, clinical translation of HSP-directed therapies has been challenged by toxicity, compensatory heat shock responses, and resistance mechanisms. Many N-terminal HSP90 inhibitors have shown clinical utility but have also highlighted the need for alternative approaches, including C-terminal inhibition, HSP70-directed therapies, and rational combination strategies targeting compensatory survival pathways. Emerging inhibitors targeting HSP27, HSP60, and HSP110, as well as HSP-based vaccines, further expand therapeutic opportunities across cancer subtypes. Collectively, these approaches highlight the growing therapeutic relevance of disrupting interconnected HSP networks rather than targeting individual chaperones in isolation. Conclusions: Future development of heat shock protein-targeted therapies will require a deeper understanding of HSP-mediated chemoresistance. Clinical trial and drug development approaches may benefit from combination or multi-targeted strategies that simultaneously disrupt multiple components of the heat shock protein network to achieve more durable anticancer responses. Full article

Infestation by boring sponges poses a serious problem for Pacific oyster Magallana gigas (Thunberg, 1793) aquaculture. This study aimed to assess the effect of Pione vastifica sponge infestation on the oysters’ capacity for shell repair, antioxidant defence status, and hemocyte functional state. We analysed the expression of VEGF pathway genes and biomineralisation enzymes, molecular chaperones (Hsp70, Hsp90), growth arrest and DNA damage gene (Gadd45α), antioxidant enzyme activity and lipid peroxidation levels in the hemolymph and various mantle parts (central and outer-edge). Intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential in hemocytes were evaluated. The results showed that infection significantly increases intracellular ROS levels in hemocytes without changing mitochondrial membrane potential. Oxidative damage was localised primarily in the central mantle contacting the damaged shell. In the outer-edge mantle responsible for shell growth, marked upregulation of SodMn, Cat, and Gadd45α was observed, coupled with suppression of VEGF-R receptor expression and organic matrix genes. Heat shock protein expression decreased in all examined tissues of infected molluscs. Our results demonstrate that shell damage induced by boring sponges triggers a tissue-specific reorganisation of physiological priorities, manifesting as a bioenergetic trade-off where limited energy resources are reallocated from the ATP-demanding process of biomineralisation to sustain antioxidant defence and cell survival. Full article

Prion diseases are caused by self-propagating and transmissible alternative conformations of certain proteins, which induce neurotoxicity and lead to transmissible spongiform encephalopathy (TSE) in mammalian. Prions were also found in fungi, and in particular, the yeast Saccharomyces cerevisiae. Manganese (Mn) is an essential nutrient and plays crucial roles in central nervous system. However, high concentration of manganese is regarded as an environmental neuronal stressor which would induce striatal neurotoxicity. Long-term exposure to high concentration of manganese would increase the proportion of the infectiously pathogenic isoform (PrPSc) of prion protein. Additionally, increase of manganese levels was found to be age-related in human brain. Here, we studied the effect of manganese on prion using budding yeast prion [URE3] as model organism. We found the exposure to manganese can enhance the de novo generation and propagation of yeast prion [URE3], as well as the expression levels of chaperones Hsp104p and Hsp70p, in a dose-dependent manner. Full article

Background: During maize anthesis, heat stress severely limits productivity—particularly under humid conditions where high humidity suppresses transpirational cooling, forcing tissues to endure direct thermal load. Methods: Using field enclosures to impose enclosure-imposed humid heat shock (EHS), we screened 135 maize inbred lines for flowering-stage yield resilience, using grain weight per ear at maturity under EHS relative to the corresponding control (CK) condition as the primary selection criterion. Based on this screen, we selected two tolerant (R025, R100) and two sensitive (R133, R135) genotypes for data-independent acquisition mass spectrometry (DIA-MS) profiling of the tassel-subtending leaf. Results: At baseline, the selected tolerant lines exhibited a constitutively distinct proteomic state, including lower abundance of light-harvesting complex components and higher abundance or detection frequency of several regulatory proteins, including SRK2E/OST1 and HSF-B2a. Under sustained EHS, the selected sensitive lines showed extensive proteomic disruption, including reduced abundance of photosynthesis-related proteins and oxidative phosphorylation, together with increased abundance of proteins associated with endoplasmic reticulum stress responses and protein turnover. In contrast, the selected tolerant lines displayed a more constrained acclimation response, characterized by relative maintenance of photosynthesis-related proteins together with selective increases in chaperone systems (HSP90/sHSPs) and benzoxazinoid biosynthesis-related proteins. Several proteins showed switch-like detection patterns between the selected tolerant and sensitive lines, including TMEM97-like and a peptidyl-prolyl isomerase, indicating potentially distinct regulatory states. Conclusions: These findings suggest that tolerant performance under enclosure-imposed heat stress is associated with a pre-conditioned proteomic state and enhanced protein homeostasis (proteostasis) buffering capacity that may help preserve photosynthetic function during flowering-stage stress. The identified proteins should be regarded as candidate markers requiring further functional validation before any application in breeding programs aimed at improving adaptation to increasingly frequent heat-stress events. Full article