Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline

Search Results (378)

Search Parameters:
Keywords = heat shock protein family A

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
17 pages, 4221 KB  
Article
Mining Thermotolerant Candidate Genes Co-Responsive to Heat Stress in Wheat Flag Leaves and Grains Using WGCNA Analysis
by Liangpeng Chen, Zhengcong Xu, Wensheng Lin, Junkang Rong and Xin Hu
Agronomy 2026, 16(3), 300; https://doi.org/10.3390/agronomy16030300 - 25 Jan 2026
Abstract
As a critically important global food crop, wheat has been increasingly threatened by the frequent occurrence of extreme high-temperature events, which impairs its growth and development, resulting in reduced seed-setting rate, compromised grain quality and diminished yield. Therefore, identifying heat-tolerant genes and enhancing [...] Read more.
As a critically important global food crop, wheat has been increasingly threatened by the frequent occurrence of extreme high-temperature events, which impairs its growth and development, resulting in reduced seed-setting rate, compromised grain quality and diminished yield. Therefore, identifying heat-tolerant genes and enhancing thermotolerance through molecular breeding are essential strategies for wheat improvement. In this study, we retrieved spatial transcriptomic data from the public database PRJNA427246, which captured gene expression profiles in flag leaves and grains of the heat-sensitive wheat cultivar Chinese Spring (CS) under 37 °C heat stress at time points of 0 min, 5 min, 10 min, 30 min, 1 h, and 4 h. Weighted Gene Co-expression Network Analysis (WGCNA) was used to construct co-expression networks for flag leaf and grain transcriptomes. One highly significant module was identified in each tissue, along with 35 hub genes that showed a strong temporal association with heat stress progression. Notably, both modules contained the previously characterized thermotolerance gene TaMBF1c, suggesting that additional heat-responsive genes may be present within these modules. Simultaneous analysis of the expression data from four groups (encompassing different tissues and high-temperature treatments) for the 35 core genes revealed that genes from the TaHSP20 family, TaMBF1c family, and other related genes exhibit coordinated expression patterns in terms of the temporal dynamics and tissue distribution of stress responses. Additionally, 27 genes of the small heat shock protein (HSP20) family are predicted to be involved in the endoplasmic reticulum-associated degradation (ERAD) pathway. They assist in clearing misfolded proteins induced by stress, thereby helping to maintain endoplasmic reticulum homeostasis and cellular functions under stress conditions. Finally, the expression levels of three core genes, TaHSP20-1, TaPCDP4, and TaMBF1c-D, were validated by qRT-PCR in two wheat cultivars with distinct thermotolerance: S116 (Zhehuamai 2008) and S128 (Yangmai 33). These findings provide new insights into the molecular mechanisms underlying heat tolerance in wheat and offer valuable genetic resources for breeding thermotolerant varieties. Full article
(This article belongs to the Special Issue Enhancing Wheat Yield Through Sustainable Farming Practices)
Show Figures

Figure 1

23 pages, 5209 KB  
Article
Genome-Wide Identification and Expression Analysis of the Hsp70 Gene Family in Hylocereus undatus Seedlings Under Heat Shock Stress
by Youjie Liu, Ke Wen, Hanyao Zhang, Xiuqing Wei, Liang Li, Ping Zhou, Yajun Tang, Dong Yu, Yueming Xiong and Jiahui Xu
Int. J. Mol. Sci. 2026, 27(2), 816; https://doi.org/10.3390/ijms27020816 - 14 Jan 2026
Viewed by 114
Abstract
Hylocereus undatus growth is limited by long-term heat stress, and heat shock protein 70 (Hsp70) is crucial in the plant’s heat stress (HS) response. In a previous study, transcriptomic data revealed that Hsp70 family members in pitaya seedlings respond to temperature changes. This [...] Read more.
Hylocereus undatus growth is limited by long-term heat stress, and heat shock protein 70 (Hsp70) is crucial in the plant’s heat stress (HS) response. In a previous study, transcriptomic data revealed that Hsp70 family members in pitaya seedlings respond to temperature changes. This study identified 27 HuHsp70 genes in pitaya, analyzed their physicochemical properties (such as molecular weight and isoelectric point), and divided them into five subfamilies with conserved gene structures, motifs (short conserved sequence patterns), and cis-acting elements (regulatory DNA sequences). The Ks value (synonymous substitution rate) ranged from 0.93~3.54, and gene duplication events occurred between 71.17 and 272.19 million years ago (Mya). Under HS, eight and nine differentially expressed genes (DEGs) were detected at 24 h and 48 h, respectively. Quantitative real-time PCR (qRT-PCR, a method for measuring gene expression) verified the expression trends, with HuHsp70-11 expression increasing with heat shock duration, indicating that HuHsp70-11 is a key candidate. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that HuHsp70s, especially HuHsp70-11, play key roles in responding to high temperatures (HT) in H. undatus seedlings. A potential model by which HuHsp70-11 removes excess reactive oxygen species (ROS) and enhances cell membrane permeability was constructed. These results provide new perspectives for exploring the HS response mechanisms and adaptability of H. undatus plants to heat stress. Full article
Show Figures

Figure 1

23 pages, 14339 KB  
Article
Integrative Genomic and Transcriptomic Analysis of White-Rot Fungi Ganoderma tsugae Growing on Both Coniferous and Broad-Leaved Trees
by Yifei Sun, Mengxue Lv, Meiqin Luo, Ziqi Yao, Miao Zhou, Yuxuan Fang, Dongmei Wu, Neng Gao and Baokai Cui
J. Fungi 2026, 12(1), 35; https://doi.org/10.3390/jof12010035 - 1 Jan 2026
Viewed by 471
Abstract
Ganoderma tsugae is a typical white-rot fungus capable of decaying both coniferous and broad-leaved trees and is also used in traditional Chinese medicine for its immunomodulatory and anticancer properties. To elucidate the molecular basis of its broad substrate adaptability, we performed integrated genomic [...] Read more.
Ganoderma tsugae is a typical white-rot fungus capable of decaying both coniferous and broad-leaved trees and is also used in traditional Chinese medicine for its immunomodulatory and anticancer properties. To elucidate the molecular basis of its broad substrate adaptability, we performed integrated genomic and transcriptomic analyses of two G. tsugae strains (collected from Xingjiang on Betula and Jilin on Larix). The high-quality genomes of G. tsugae Wu 2022 from Xinjiang (40.8 Mb, 12,496 genes) and G. tsugae Cui 14110 from Jilin (45.6 Mb, 13,450 genes) were obtained. There are enriched gene families related to carbohydrate-active enzymes (CAZymes) in two G. tsugae strains. Notably, specific CAZyme families implicated in hemicellulose (GH16), chitin metabolism (GH18), and ester bond cleavage (CE10) were prominently expanded. Transcriptome analyses under the induction of Betula and Larix sawdust revealed a core adaptive response. A total of 5558 genes were differentially expressed, including 2094 up-regulated and 3464 down-regulated genes. Most differentially expressed genes (DEGs) were annotated as “catalytic activity”, “metabolic processes” and specific functions such as nutrient transport (“MFS transporter”), and lipid metabolism (“3-oxoacyl-[acyl-carrier protein] reductase”). In addition, a conserved suite of the eleven shared DEGs were annotated as “Heat shock protein 9/12”, “alcohol dehydrogenase”, and “Cytochrome p450” related to secondary metabolites biosynthesis, transport, and catabolism. Based on the annotation results, the wood degradation mechanism of G. tsugae can be described as synthesizing and secreting degradation enzyme system to obtain energy, using protective enzyme systems to ensure its own health, and employing a transport enzyme system to recycle metabolic capacity. This progress ensures the environmental adaptability and high degradation efficiency of G. tsugae during wood degradation. Full article
(This article belongs to the Special Issue Fungal Metabolomics and Genomics, 2nd Edition)
Show Figures

Figure 1

16 pages, 604 KB  
Article
Expression of the 60 and 70 kDa Family of Heat Shock Proteins in Trachea Epithelium Cells of Poults Experiencing Bordetellosis
by Frank W. Edens
Poultry 2026, 5(1), 5; https://doi.org/10.3390/poultry5010005 - 1 Jan 2026
Viewed by 211
Abstract
Heat shock protein (HSP) gene families are known to be expressed preferentially over normal cellular proteins when poultry cells are exposed to environmental stressors. Bordetella avium infection leads to bordetellosis, which is characterized by severe inflammation of the tracheal epithelium, representing a severe [...] Read more.
Heat shock protein (HSP) gene families are known to be expressed preferentially over normal cellular proteins when poultry cells are exposed to environmental stressors. Bordetella avium infection leads to bordetellosis, which is characterized by severe inflammation of the tracheal epithelium, representing a severe stressor for the infected turkey poult. The purpose of this experiment was to examine the expression of HSP60 and HSP70 in the tracheae of B. avium-challenged poults. Tracheae were dissected from five poults per treatment at 7, 11, 14, and 21 days of age, and snap-frozen rings were examined immunohistochemically for the presence of HSP60 and HSP70 using HSP60 and HSP70 monoclonal antibodies (MABs). Infected poults expressed HSP60 predominantly on the apical surface of ciliated epithelial cells and weakly near the nucleus, and HSP70 was expressed only in the cytoplasm. Early in the development of bordetellosis, infected poults expressed more HSP60 and HSP70 than control poults of the same age, but at 14 days after infection, infected birds showed significantly decreased HSP60 proteins, which was associated with loss of tracheal epithelium. With loss of tracheal epithelium, the expression of HSP70 decreased at 11 days in the infected poults, and by day 21, very low levels of the proteins were observed in the infected poults compared to control poults with intact tracheal epithelium. It was concluded that decreased expression of HSP60 was indicative of HSP60 proteins becoming antigenic targets for the host’s immune system since immunologically targeted B. avium cells express GroEL (highly conserved HSP60 family equivalent) and DnaK (highly conserved HSP70 equivalent). The potential targeting of host and pathogen HSP60 by the innate immune system could feasibly facilitate loss of tracheal epithelium during the development of bordetellosis. Full article
Show Figures

Figure 1

15 pages, 1399 KB  
Article
Antibodies Against SARS-CoV-2 Nucleocapsid Protein Possess Autoimmune Properties
by Alexandra Rak, Yana Zabrodskaya, Pei-Fong Wong and Irina Isakova-Sivak
Antibodies 2026, 15(1), 2; https://doi.org/10.3390/antib15010002 - 22 Dec 2025
Viewed by 905
Abstract
Background/Objectives: Notwithstanding the declaration by the World Health Organization in May 2023 regarding the conclusion of the COVID-19 pandemic, new cases of this potentially lethal infection continue to be documented globally, exerting a sustained influence on the worldwide economy and social structures. Contemporary [...] Read more.
Background/Objectives: Notwithstanding the declaration by the World Health Organization in May 2023 regarding the conclusion of the COVID-19 pandemic, new cases of this potentially lethal infection continue to be documented globally, exerting a sustained influence on the worldwide economy and social structures. Contemporary SARS-CoV-2 variants, while associated with a reduced propensity for severe acute pathology, retain the capacity to induce long-term post-COVID syndrome, including in ambulatory patient populations. This clinical phenomenon may be attributable to potential autoimmune reactions hypothetically triggered by antiviral antibodies, thereby underscoring the need for developing novel, universal vaccines against COVID-19. The nucleocapsid protein (N), being one of its most conserved and highly immunogenic components of SARS-CoV-2, presents a promising target for such investigative efforts. However, the protective role of anti-N antibodies, generated during natural infection or through immunization with N-based vaccines, alongside the potential adverse effects associated with their production, remains to be fully elucidated. In the present study, we aim to identify potential sites of homology in structures or sequences between the SARS-CoV-2 N protein and human antigens detected using hyperimmune sera against N protein obtained from mice, rabbits, and hamsters. Methods: We employed Western blot analysis of lysates from human cell lines (MCF7, HEK293T, THP-1, CaCo2, Hep2, T98G, A549) coupled with mass spectrometric identification to assess the cross-reactivity of polyclonal and monoclonal antibodies generated against recombinant SARS-CoV-2 N protein with human self-antigens. Results: We showed that anti-N antibodies developed in mice and rabbits exhibit pronounced immunoreactivity towards specific components of the human proteome. In contrast, anti-N immunoglobulins from hamsters showed no non-specific cross-reactivity with either hamster or human proteomic extracts because of the lack of autoreactivity or immunogenicity differences. Subsequent mass spectrometric analysis of the immunoreactive bands identified principal autoantigenic targets, which were predominantly heat shock proteins (including HSP90-beta, HSP70, mitochondrial HSP60, and HSPA8), histones (H2B, H3.1–3), and key metabolic enzymes (G6PD, GP3, PKM, members of the 1st family of aldo-keto reductases). Conclusions: The results obtained herein highlight the differences in the development of anti-N humoral responses in humans and in the Syrian hamster model. These data provide a foundational basis for formulating clinical recommendations to predict possible autoimmune consequences in COVID-19 convalescents and are of critical importance for the rational design of future N protein-based, cross-protective vaccine candidates against novel coronavirus infections. Full article
(This article belongs to the Section Humoral Immunity)
Show Figures

Figure 1

20 pages, 3460 KB  
Article
Comparative Thermal Tolerance and Tissue-Specific Responses Patterns to Gradual Heat Stress in Reciprocal Cross Hybrids of Acipenser baerii and A. schrenckii
by Wei Wang, Linan Gao, Xiaoyu Yan, Wenjie Liu, Tian Dong, Hailiang Song, Guoqing Ma and Hongxia Hu
Int. J. Mol. Sci. 2026, 27(1), 132; https://doi.org/10.3390/ijms27010132 - 22 Dec 2025
Viewed by 296
Abstract
The increasing frequency and intensity of heatwaves due to climate change pose significant challenges to sturgeon aquaculture. This study investigated the effects of gradual heat stress (1 °C every 8 h) on two reciprocal hybrid sturgeon strains (Acipenser baerii ♀ × A. [...] Read more.
The increasing frequency and intensity of heatwaves due to climate change pose significant challenges to sturgeon aquaculture. This study investigated the effects of gradual heat stress (1 °C every 8 h) on two reciprocal hybrid sturgeon strains (Acipenser baerii ♀ × A. schrenckii ♂, (BS hybrid); A. schrenckii ♀ × A. baerii ♂, (SB hybrid)), focusing on their antioxidant defense mechanisms, heat shock protein (HSP) expression, and liver and gill tissue histology. When water temperature raised to 34.3 °C (about 104 h), LOE (loss of equilibrium) individuals appeared. Twenty-four hours after sampling, fifteen BS hybrid sturgeon remained alive, whereas no SB hybrid sturgeon survived. In this study, the slow heat stress significantly elevated the expression of HSP-related genes (hsc70, hsp70, hsp90) in both the liver of BS hybrid sturgeon and the gills of SB hybrid sturgeon. However, in the gills of BS hybrid sturgeon and the liver of SB hybrid sturgeon, the expression of hsp family genes in the experimental groups was either lower than or comparable to the control group. Significant liver damage, including cellular vacuolization and necrosis, was observed in BS hybrids, while SB hybrid sturgeon exhibited more pronounced gill tissue damage. Among the four antioxidant enzymes—superoxide dismutase (SOD), lactate dehydrogenase (LDH), catalase (CAT) glutathione peroxidase (GPx)—only LDH activity was elevated in the hepatic tissue of BS hybrid sturgeon, corresponding to increased serum lactate levels, while gill LDH activity was higher in SB hybrid sturgeon. In both hybrids, LDH activity exhibited an increasing trend in the kidney. However, total antioxidant capacity (T-AOC) remained unchanged across all three tissues. Both plasma cortisol and lactate were substantially affected by thermal stress. MDA remained at a relatively stable level after heat stress and recovery. These results demonstrate differential tissue-specific responses to heat stress in the reciprocal hybrids. More importantly, the BS hybrid sturgeon exhibited significantly higher thermal tolerance and post-stress survival compared to the SB hybrid sturgeon. These findings reveal that the choice of maternal parent is a critical factor influencing heat resistance in these hybrids, providing a key basis for selective breeding programs and optimizing aquaculture management. Full article
Show Figures

Figure 1

19 pages, 1606 KB  
Review
The GHKL ATPase Family as a Paradigm for MutL Homolog Function in DNA Mismatch Repair
by Jonathan M. Piscitelli and Carol M. Manhart
Int. J. Mol. Sci. 2025, 26(24), 12157; https://doi.org/10.3390/ijms262412157 - 18 Dec 2025
Viewed by 331
Abstract
ATP hydrolysis drives essential processes across biology, from nucleic acid translocation and conformational switching to signal transduction. The GHKL ATPase family—DNA Gyrase B, Heat Shock Protein 90 (Hsp90), Histidine Kinases, and MutL homologs—shares a Bergerat-fold that couples nucleotide binding and hydrolysis to conformational [...] Read more.
ATP hydrolysis drives essential processes across biology, from nucleic acid translocation and conformational switching to signal transduction. The GHKL ATPase family—DNA Gyrase B, Heat Shock Protein 90 (Hsp90), Histidine Kinases, and MutL homologs—shares a Bergerat-fold that couples nucleotide binding and hydrolysis to conformational changes, dimerization, and signaling. Despite their diverse roles, GHKL proteins rely on common ATP-dependent principles. Within this family, MutLα (MLH1-PMS2 in humans, Mlh1-Pms1 in yeast) is central to eukaryotic mismatch repair, where it provides the endonuclease activity needed for strand incision and coordinates interactions with other repair partners. MutLα exemplifies how the Bergerat-fold has been adapted to regulate DNA interactions, partner communication, and protein turnover on DNA. By examining MutLα through the lens of other GHKL proteins, we can clarify how ATP binding and hydrolysis drive its conformational dynamics, nuclease activation, and regulation within its pathway, highlighting how conserved mechanistic strategies are repurposed across biological systems. Full article
(This article belongs to the Special Issue Molecular Mechanism in DNA Replication and Repair)
Show Figures

Figure 1

29 pages, 870 KB  
Review
Epigenomics and Non-Coding RNAs in Soybean Adaptation to Abiotic Stresses
by Kinga Moskal, Bartosz Tomaszewski and Maja Boczkowska
Int. J. Mol. Sci. 2025, 26(23), 11527; https://doi.org/10.3390/ijms262311527 - 27 Nov 2025
Viewed by 685
Abstract
This review presents soybean responses to drought, heat, and salinity within a signal–transcript–chromatin framework. In this framework, calcium/reactive oxygen species and abscisic acid cues converge on abscisic acid-responsive element binding factor (ABF/AREB), dehydration-responsive element binding protein (DREB), NAC, and heat shock factor (HSF) [...] Read more.
This review presents soybean responses to drought, heat, and salinity within a signal–transcript–chromatin framework. In this framework, calcium/reactive oxygen species and abscisic acid cues converge on abscisic acid-responsive element binding factor (ABF/AREB), dehydration-responsive element binding protein (DREB), NAC, and heat shock factor (HSF) families. These processes are modulated by locus-specific chromatin and non-coding RNA layers. Base-resolved methylomes reveal a high level of CG methylation in the gene body, strong CHG methylation in heterochromatin, and dynamic CHH ‘islands’ at the borders of transposable elements. CHH methylation increases over that of transposable elements during seed development, and GmDMEa editing is associated with seed size. Chromatin studies in soybean and model species implicate the reconfiguration of salt-responsive histone H3 lysine 27 trimethylation (H3K27me3) in G. max and heat-linked H2A.Z dynamics at thermoresponsive promoters characterized in Arabidopsis and other plants, suggesting that a conserved chromatin layer likely operates in soybean. miR169–NF-YA, miR398–Cu/Zn Superoxide Dismutases(CSD)/copper chaperone of CSD(CCS), miR393–transporter inhibitor response1/auxin signaling F-box (TIR1/AFB), and miR396–growth regulating factors (GRF) operate across leaves, roots, and nodules. Overexpression of lncRNA77580 enhances drought tolerance, but with context-dependent trade-offs under salinity. Single-nucleus and spatial atlases anchor these circuits in cell types and microenvironments relevant to stress and symbiosis. We present translational routes, sentinel epimarkers (bisulfite amplicons, CUT&Tag), haplotype-by-epigenotype prediction, and precise cis-regulatory editing to accelerate marker development, genomic prediction and the breeding of resilient soybean varieties with stable yields. Full article
Show Figures

Graphical abstract

13 pages, 9466 KB  
Article
Functional Analysis of the Role Played by the MiHSP90 Gene Family in the Shell Thickness of Macadamia Nuts (Macadamia integrifolia)
by Xiuju Huan, Qiujin Tan, Xiuhua Tang, Chunheng Zhou, Xiaozhou Yang, Yuanrong Wei, Haisheng Chen, Wenlin Wang and Lifeng Wang
Forests 2025, 16(12), 1775; https://doi.org/10.3390/f16121775 - 25 Nov 2025
Viewed by 339
Abstract
Macadamia integrifolia is a vital cash crop. The shells of its nuts serve multiple purposes in both agricultural practices and waste management initiatives. In this research, transcriptome analysis was carried out on three macadamia nut varieties with significantly different shell thicknesses, namely ‘A38’, [...] Read more.
Macadamia integrifolia is a vital cash crop. The shells of its nuts serve multiple purposes in both agricultural practices and waste management initiatives. In this research, transcriptome analysis was carried out on three macadamia nut varieties with significantly different shell thicknesses, namely ‘A38’, ‘Guire No.1’ (‘GR1’), and HAES842 (‘842’), at the same stage of maturity. The results revealed remarkable differences in their gene expression profiles. A total of 4311 novel genes were identified, among which 1631 were functionally annotated. Analyses using Gene Ontology (GO), Clusters of Orthologous Groups (COGs), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that the main categories of differentially expressed genes (DEGs) were associated with plant–pathogen interactions. Additionally, 10 members of the heat shock protein 90 (MiHSP90) family were identified and classified into subgroups A, B, and C by comparing them with the HSP90 gene family members of Arabidopsis and rice. Among these, the MiHSP90.1, MiHSP90.2, and MiHSP90.9 proteins were differentially highly expressed in the three macadamia nut varieties. These findings provide fundamental insights into the regulatory mechanisms underlying shell formation in macadamia nuts. Full article
(This article belongs to the Section Genetics and Molecular Biology)
Show Figures

Figure 1

13 pages, 3119 KB  
Article
Characterization and Evolutionary Analysis of Non-Canonical Heat Shock Protein 70 Family Members in Metazoan
by Jiabo Tan, Xiaohan Li, Qi Wang, Weiqi Xu, Jixiang Liu, Yunlong He, Wenhui Yin, Jiahao Li, Xinyu Li, Xiaojun Song, Kefeng Xu and Guodong Wang
Int. J. Mol. Sci. 2025, 26(23), 11363; https://doi.org/10.3390/ijms262311363 - 24 Nov 2025
Viewed by 388
Abstract
To broaden the scope of research on the characteristics and evolutionary relationships within the heat shock protein 70 (Hsp70) family, encompassing its non-canonical members, amino acid sequences of Hsp70-12, Hsp70-13, and Hsp70-14, alongside those of traditional Hsp70, were collected and analyzed. The findings [...] Read more.
To broaden the scope of research on the characteristics and evolutionary relationships within the heat shock protein 70 (Hsp70) family, encompassing its non-canonical members, amino acid sequences of Hsp70-12, Hsp70-13, and Hsp70-14, alongside those of traditional Hsp70, were collected and analyzed. The findings indicate that, during the evolution of metazoans, the various Hsp70 groups diverged from one another. Specifically, Hsp70-12 emerges as the least conserved member, as evidenced by structural alignment data and the Ka/Ks ratio. It not only represents the most distantly related group to traditional Hsp70 but also stands out as the sole alkaline group within the family. In contrast, Hsp70-13 exhibits a close evolutionary relationship with traditional Hsp70, albeit with the notable loss of its C-terminal domain. Hsp70-14 occupies an intermediate position between Hsp70-12 and Hsp70-13. Phylogenetic analysis suggests that these groups diverged prior to the advent of invertebrates. Furthermore, five conserved motifs within the ATP-binding domain of Hsp70, which serve as distinguishing features for Hsp70 groups, were identified. The diverse characters of the non-canonical Hsp70s are probably related to their special cellular location and tissue specificity. Together, the results of this research will help identify and categorize Hsp70s. Further research that aims at identifying additional non-canonical Hsp70 members and elucidating the distinct characteristics and functions of these molecular chaperones will enhance our comprehension of the origin and evolutionary trajectory of the Hsp70 family. Full article
(This article belongs to the Section Molecular Biology)
Show Figures

Figure 1

28 pages, 1773 KB  
Review
Heat Shock Protein Chaperome Is a Multi-Faceted Vector for Tumor Cell Migratory Activity, Invasion, and Metastasis
by Viacheslav Fedorov, Andrey Kurkin, Georgii Fofanov, Vitaliya Kaneva, Anna Kondratenko, Stephanie E. Combs and Maxim Shevtsov
Cells 2025, 14(23), 1837; https://doi.org/10.3390/cells14231837 - 21 Nov 2025
Viewed by 828
Abstract
Heat shock proteins (HSPs), in particular, representatives of the HSP70 and HSP90 families, are the folding centers of cell proteins and have been proven to be overexpressed in various types of solid and hematological malignancies. With their involvement in a number of cellular [...] Read more.
Heat shock proteins (HSPs), in particular, representatives of the HSP70 and HSP90 families, are the folding centers of cell proteins and have been proven to be overexpressed in various types of solid and hematological malignancies. With their involvement in a number of cellular functions (e.g., protection from various stresses including radiochemotherapy, transport regulation, apoptotic signal inhibition, etc.), these chaperones are a valuable target for cancer progression research. However, recent focus has shifted to the HSP interaction network, which includes many molecules involved in cell migration and invasion pathways. Investigating the interplay between different co-chaperones and their effect on cell motility may help with establishing a palette of available diagnostic and therapeutic targets for highly invasive cancer types. In this review, we describe current models of the HSP functional cycle and recent studies proving links between these cycle regulators and contributions to cell migration. Based on detailed studies of various co-chaperones’ involvement in cancer progression, the network approach gives much necessary molecular context to previously established HSP functions. Full article
Show Figures

Figure 1

24 pages, 4270 KB  
Article
HSPA5, a Host Cellular Heat-Shock Protein Required for Influenza a Virus Replication
by Mahamud-ur Rashid, Tamanna Yasmin and Kevin M. Coombs
Int. J. Mol. Sci. 2025, 26(22), 10998; https://doi.org/10.3390/ijms262210998 - 13 Nov 2025
Viewed by 749
Abstract
The Influenza A Virus (IAV) is known to hijack cellular proteins during its replication. IAV infection increases the expression of Heat-shock-protein family A (Hsp70) member 5 (HSPA5) in human cells, but its specific function in the viral life cycle remains unclear. This study [...] Read more.
The Influenza A Virus (IAV) is known to hijack cellular proteins during its replication. IAV infection increases the expression of Heat-shock-protein family A (Hsp70) member 5 (HSPA5) in human cells, but its specific function in the viral life cycle remains unclear. This study aims to elucidate the function of HSPA5 in IAV replication, by implementing HSPA5 knockdown (KD) in A549 cells and assessing its impact on IAV’s viral protein translation, genomic RNA transcription, and the host cellular proteome. HSPA5 KD significantly reduced progeny virus release, although viral RNA levels were unaffected. Interestingly, levels of viral structural proteins increased in HSPA5 KD cells after infection. Treatment with HSPA5 inhibitor also suppressed IAV replication, confirming its role as a host dependency factor. Proteomic profiling revealed 116 proteins altered in wild-type cells and 223 in HSPA5 KD cells, with 32 uniquely dysregulated in wild-type and 139 unique to HSPA5 KD cells. In HSPA5 knockdown cells, the altered proteins were linked to pathways such as EIF2, EGF, PEDF, CNTF, IL-13, and G-protein receptor signaling, as well as to cellular processes like lymphocyte activation and regulation of immune and blood cell death, which were not affected in wild-type cells after IAV infection. Overall, this study suggests that HSPA5 contributes to late stages of IAV replication, likely assembly or maturation, and represents a promising target for antiviral drug development. Full article
(This article belongs to the Special Issue Role of Proteomics in Human Diseases and Infections)
Show Figures

Figure 1

21 pages, 6032 KB  
Article
Characterization of With-No-Lysine Kinase Family Genes and Roles of CaWNK6 in the Heat Tolerance of Pepper (Capsicum annuum L.)
by Jianwei Zhang, Libo Liu, Jianxin Fan, Yao Jiang, Xianjun Chen, Qin Yang and Huanxiu Li
Plants 2025, 14(22), 3430; https://doi.org/10.3390/plants14223430 - 9 Nov 2025
Viewed by 594
Abstract
With-No-Lysine (WNK) kinases constitute a subgroup within the serine/threonine protein kinase family, characterized by the absence of a catalytic lysine residue in the kinase subdomain II located in their N-terminal region. These kinases play critical roles in regulating plant growth, development, and responses [...] Read more.
With-No-Lysine (WNK) kinases constitute a subgroup within the serine/threonine protein kinase family, characterized by the absence of a catalytic lysine residue in the kinase subdomain II located in their N-terminal region. These kinases play critical roles in regulating plant growth, development, and responses to abiotic stressors. However, members of the WNK and their responses to heat stress in pepper (Capsicum annuum L.) remain unexplored. In the present study, we identified eleven WNK genes within the genome of pepper cultivar ‘UCD-10X-F1’ and designated them CaWNK1 to CaWNK11 according to their chromosomal positions. Comprehensive analyses were conducted to elucidate their phylogenetic relationships, chromosomal distribution, collinearity, gene structure, protein properties, and cis-acting elements within promoter regions. The findings revealed that the CaWNK gene family segregates into five distinct subgroups. Comparative genomic analysis identified eleven and nine segmental duplication gene pairs between pepper and tomato and between pepper and Arabidopsis, respectively. Within the pepper genome, two pairs of segmentally duplicated genes and two pairs of tandemly repeated genes were also detected. The CaWNK gene sequences in pepper exhibited a high degree of conservation; however, variations were observed in the number of introns and exons. Analysis of the promoter regions revealed an abundance of cis-acting elements associated with growth and development, stress responses, and hormone regulation. Subsequent transcriptomic analyses demonstrated that CaWNK genes displayed tissue-specific expression patterns and differential expression levels following treatments with exogenous plant hormones and abiotic stresses. Notably, the expression of CaWNK6 was significantly up-regulated under heat stress conditions. To elucidate the functional role of CaWNK6, virus-induced gene silencing (VIGS) was employed to suppress its expression in pepper seedlings. Silencing of CaWNK6 resulted in disrupted tissue architecture, stomatal closure, and diminished heat tolerance. These phenotypic changes correlated with excessive accumulation of reactive oxygen species (ROS), reduced activity of antioxidant enzymes, and down-regulation of heat shock factor (HSF) genes in the silenced plants. Collectively, these findings offer valuable insights into the functional roles of CaWNK genes and hold significant implications for the development of novel heat-tolerant pepper cultivars. Full article
(This article belongs to the Section Plant Response to Abiotic Stress and Climate Change)
Show Figures

Figure 1

37 pages, 2625 KB  
Review
Beyond Folding: Expanding the Functional Landscape of Hsp90 Chaperone Machinery in Health and Disease
by Manish Kumar Singh, Jyotsna S. Ranbhise, Minghao Fu, Songhyun Ju, Sunhee Han, Hyeong Rok Yun, Wonchae Choe, Sung Soo Kim and Insug Kang
Int. J. Mol. Sci. 2025, 26(21), 10279; https://doi.org/10.3390/ijms262110279 - 22 Oct 2025
Cited by 3 | Viewed by 1685
Abstract
Molecular chaperones are crucial for maintaining protein homeostasis by assisting in the proper folding, stabilization, and function of proteins. Among them, Heat shock protein 90 (Hsp90), represents a highly conserved protein family of molecular chaperones that plays an essential role in diverse biological [...] Read more.
Molecular chaperones are crucial for maintaining protein homeostasis by assisting in the proper folding, stabilization, and function of proteins. Among them, Heat shock protein 90 (Hsp90), represents a highly conserved protein family of molecular chaperones that plays an essential role in diverse biological processes and is fundamental to cellular health and survival. As a highly abundant molecular chaperone, Hsp90 comprises 1–2% of cellular proteins, increasing to 4–6% under stress conditions. It interacts with client proteins, assisting them in proper folding and stability. Unlike classical chaperonins, Hsp90 operates through a highly regulated, ATP-dependent cycle that involves multiple co-chaperones. This process allows Hsp90 to selectively engage with numerous client proteins, including signaling proteins, kinases, hormone receptors, and transcription factors. Recent discoveries have revealed its involvement in processes beyond protein folding, demonstrating its role in diverse cellular functions such as epigenetic regulation, immune signaling, and oncogenic transformation. This current review highlighted the specific characteristics of cytoplasmic and endoplasmic reticulum (ER) as well as mitochondrial paralogs and functions, focusing on its contribution to buffering genetic variation, facilitating oncogene addiction, and modulating disease phenotypes in conditions such as cancer, neurodegeneration, cardiovascular diseases (CVD), and diabetes. We also discuss the therapeutic potential of targeting Hsp90 and its co-chaperones, outlining the challenges and prospects in drug development. These insights not only reshape our understanding of chaperone biology but also present opportunities for precision medicine in various human diseases. Full article
(This article belongs to the Section Macromolecules)
Show Figures

Figure 1

14 pages, 2863 KB  
Article
HSPA1A Can Alleviate CFA-Induced Inflammatory Pain by Modulating Macrophages
by Wenjie Zhang, Xiaojun Xie, Xiaomin Xiong and Feiyu Chen
Int. J. Mol. Sci. 2025, 26(19), 9591; https://doi.org/10.3390/ijms26199591 - 1 Oct 2025
Viewed by 924
Abstract
Current clinical approaches for managing inflammatory pain are frequently accompanied by adverse effects, significantly compromising patients’ quality of life. This study investigates the analgesic potential of Heat Shock Protein Family A Member 1A (HSPA1A) in alleviating Complete Freund’s Adjuvant (CFA)-induced inflammatory pain. The [...] Read more.
Current clinical approaches for managing inflammatory pain are frequently accompanied by adverse effects, significantly compromising patients’ quality of life. This study investigates the analgesic potential of Heat Shock Protein Family A Member 1A (HSPA1A) in alleviating Complete Freund’s Adjuvant (CFA)-induced inflammatory pain. The immunomodulatory mechanisms were elucidated through behavioral studies, flow cytometry, transcriptomics, proteomics, and cellular metabolic analyses. Findings indicate that HSPA1A mitigates CFA-induced mechanical allodynia, an effect independent of T or B lymphocytes and neutrophils but positively correlated with macrophage abundance. Transcriptomic RNA sequencing suggests involvement of inflammation-associated pathways. In vitro experiments demonstrate that HSPA1A suppresses the polarization of bone marrow-derived macrophages toward the pro-inflammatory M1 phenotype in an inflammatory model, with decreased mRNA expression of pro-inflammatory cytokines Interleukin-1β (Il1b) and Tumor Necrosis Factor (TNF). Macrophage metabolism undergoes reprogramming, characterized by reduced glycolysis and enhanced oxidative phosphorylation. Proteomic pathway analysis reveals suppression of pro-inflammatory and glycolytic proteins, coupled with upregulation of anti-inflammatory and tricarboxylic acid cycle-related proteins. In summary, HSPA1A likely exerts its analgesic effects by inhibiting glycolysis in macrophages, providing novel insights into inflammatory pain management and highlighting potential therapeutic targets for future clinical drug development with substantial translational potential. Full article
(This article belongs to the Section Molecular Immunology)
Show Figures

Figure 1

Back to TopTop