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Genes Aug 2022The J-proteins, also called DNAJ-proteins or heat shock protein 40 (HSP40), are one of the famous molecular chaperones. J-proteins, HSP70s and other chaperones work... (Review)
Review
The J-proteins, also called DNAJ-proteins or heat shock protein 40 (HSP40), are one of the famous molecular chaperones. J-proteins, HSP70s and other chaperones work together as constitute ubiquitous types of molecular chaperone complex, which function in a wide variety of physiological processes. J-proteins are widely distributed in major cellular compartments. In the chloroplast of higher plants, around 18 J-proteins and multiple J-like proteins are present; however, the functions of most of them remain unclear. During the last few years, important progress has been made in the research on their roles in plants. There is increasing evidence that the chloroplast J-proteins play essential roles in chloroplast development, photosynthesis, seed germination and stress response. Here, we summarize recent research advances on the roles of J-proteins in the chloroplast, and discuss the open questions that remain in this field.
Topics: Chloroplast Proteins; Chloroplasts; HSP70 Heat-Shock Proteins; Molecular Chaperones; Plants
PubMed: 36011380
DOI: 10.3390/genes13081469 -
Journal of Microbiology (Seoul, Korea) Nov 2022Pseudomonas is widespread in various environmental and host niches. To promote rejuvenation, cellular protein homeostasis must be finely tuned in response to diverse... (Review)
Review
Pseudomonas is widespread in various environmental and host niches. To promote rejuvenation, cellular protein homeostasis must be finely tuned in response to diverse stresses, such as extremely high and low temperatures, oxidative stress, and desiccation, which can result in protein homeostasis imbalance. Molecular chaperones function as key components that aid protein folding and prevent protein denaturation. Pseudomonas, an ecologically important bacterial genus, includes human and plant pathogens as well as growth-promoting symbionts and species useful for bioremediation. In this review, we focus on protein quality control systems, particularly molecular chaperones, in ecologically diverse species of Pseudomonas, including the opportunistic human pathogen Pseudomonas aeruginosa, the plant pathogen Pseudomonas syringae, the soil species Pseudomonas putida, and the psychrophilic Pseudomonas antarctica.
Topics: Humans; Pseudomonas syringae; Molecular Chaperones; Pseudomonas aeruginosa; Plants; Biodegradation, Environmental
PubMed: 36318358
DOI: 10.1007/s12275-022-2425-0 -
DNA and Cell Biology Oct 2023Heat shock protein 90 (HSP90) family is a class of proteins known as molecular chaperones that promote client protein folding and translocation in unstressed cells and... (Review)
Review
Heat shock protein 90 (HSP90) family is a class of proteins known as molecular chaperones that promote client protein folding and translocation in unstressed cells and regulate cellular homeostasis in the stress response. Noncoding RNAs (ncRNAs) are defined as RNAs that do not encode proteins. Previous studies have shown that ncRNAs are key regulators of multiple fundamental cellular processes, such as development, differentiation, proliferation, transcription, post-transcriptional modifications, apoptosis, and cell metabolism. It is known that ncRNAs do not act alone but function via the interactions with other molecules, including co-chaperones, RNAs, DNAs, and so on. As a kind of molecular chaperone, HSP90 is also involved in many biological procedures of ncRNAs. In this review, we systematically analyze the impact of HSP90 on various kinds of ncRNAs, including their synthesis and function, and how ncRNAs influence HSP90 directly and indirectly.
Topics: Humans; HSP90 Heat-Shock Proteins; Molecular Chaperones; RNA, Untranslated
PubMed: 37638805
DOI: 10.1089/dna.2023.0172 -
Cells Aug 2022Assuring a healthy proteome is indispensable for survival and organismal health. Proteome disbalance and the loss of the proteostasis buffer are hallmarks of various... (Review)
Review
Assuring a healthy proteome is indispensable for survival and organismal health. Proteome disbalance and the loss of the proteostasis buffer are hallmarks of various diseases. The essential molecular chaperone Hsp90 is a regulator of the heat shock response via HSF1 and a stabilizer of a plethora of signaling proteins. In this review, we summarize the role of Hsp90 in the cellular and organismal regulation of proteome maintenance.
Topics: HSP90 Heat-Shock Proteins; Heat-Shock Response; Molecular Chaperones; Proteome; Proteostasis
PubMed: 36010556
DOI: 10.3390/cells11162479 -
Biochemical Society Transactions Aug 2020The efficacy of superoxide dismutase-1 (SOD1) folding impacts neuronal loss in motor system neurodegenerative diseases. Mutations can prevent SOD1 post-translational... (Review)
Review
The efficacy of superoxide dismutase-1 (SOD1) folding impacts neuronal loss in motor system neurodegenerative diseases. Mutations can prevent SOD1 post-translational processing leading to misfolding and cytoplasmic aggregation in familial amyotrophic lateral sclerosis (ALS). Evidence of immature, wild-type SOD1 misfolding has also been observed in sporadic ALS, non-SOD1 familial ALS and Parkinson's disease. The copper chaperone for SOD1 (hCCS) is a dedicated and specific chaperone that assists SOD1 folding and maturation to produce the active enzyme. Misfolded or misfolding prone SOD1 also interacts with heat shock proteins and macrophage migration inhibitory factor to aid folding, refolding or degradation. Recognition of specific SOD1 structures by the molecular chaperone network and timely dissociation of SOD1-chaperone complexes are, therefore, important steps in SOD1 processing. Harnessing these interactions for therapeutic benefit is actively pursued as is the modulation of SOD1 behaviour with pharmacological and peptide chaperones. This review highlights the structural and mechanistic aspects of a selection of SOD1-chaperone interactions together with their impact on disease models.
Topics: Animals; Copper; Heat-Shock Proteins; Humans; Macrophage Migration-Inhibitory Factors; Molecular Chaperones; Mutation; Protein Folding; Superoxide Dismutase-1
PubMed: 32794552
DOI: 10.1042/BST20200318 -
Journal of Translational Medicine Mar 2021Glucose-regulating protein 78 (GRP78) is a molecular chaperone in the endoplasmic reticulum (ER) that promotes folding and assembly of proteins, controls the quality of... (Review)
Review
Glucose-regulating protein 78 (GRP78) is a molecular chaperone in the endoplasmic reticulum (ER) that promotes folding and assembly of proteins, controls the quality of proteins, and regulates ER stress signaling through Ca binding to the ER. In tumors, GRP78 is often upregulated, acting as a central stress sensor that senses and adapts to changes in the tumor microenvironment, mediating ER stress of cancer cells under various stimulations of the microenvironment to trigger the folding protein response. Increasing evidence has shown that GRP78 is closely associated with the progression and poor prognosis of lung cancer, and plays an important role in the treatment of lung cancer. Herein, we reviewed for the first time the functions and mechanisms of GRP78 in the pathological processes of lung cancer, including tumorigenesis, apoptosis, autophagy, progression, and drug resistance, giving a comprehensive understanding of the function of GRP78 in lung cancer. In addition, we also discussed the potential role of GRP78 as a prognostic biomarker and therapeutic target for lung cancer, which is conducive to improving the assessment of lung cancer and the development of new therapeutic interventions.
Topics: Apoptosis; Endoplasmic Reticulum; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Heat-Shock Proteins; Humans; Lung Neoplasms; Molecular Chaperones; Tumor Microenvironment; Unfolded Protein Response
PubMed: 33743739
DOI: 10.1186/s12967-021-02786-6 -
Annual Review of Biochemistry Jun 2021Collagen is the most abundant protein in mammals. A unique feature of collagen is its triple-helical structure formed by the Gly-Xaa-Yaa repeats. Three single chains of... (Review)
Review
Collagen is the most abundant protein in mammals. A unique feature of collagen is its triple-helical structure formed by the Gly-Xaa-Yaa repeats. Three single chains of procollagen make a trimer, and the triple-helical structure is then folded in the endoplasmic reticulum (ER). This unique structure is essential for collagen's functions in vivo, including imparting bone strength, allowing signal transduction, and forming basement membranes. The triple-helical structure of procollagen is stabilized by posttranslational modifications and intermolecular interactions, but collagen is labile even at normal body temperature. Heat shock protein 47 (Hsp47) is a collagen-specific molecular chaperone residing in the ER that plays a pivotal role in collagen biosynthesis and quality control of procollagen in the ER. Mutations that affect the triple-helical structure or result in loss of Hsp47 activity cause the destabilization of procollagen, which is then degraded by autophagy. In this review, we present the current state of the field regarding quality control of procollagen.
Topics: Animals; Collagen; Endoplasmic Reticulum; Fibrosis; HSP47 Heat-Shock Proteins; Humans; Hydroxylation; Molecular Chaperones; Procollagen; Proline; Protein Conformation; Protein Folding; Protein Processing, Post-Translational
PubMed: 33823651
DOI: 10.1146/annurev-biochem-013118-111603 -
Biochimica Et Biophysica Acta Jan 2016The findings that α-crystallins are multi-functional proteins with diverse biological functions have generated considerable interest in understanding their role in... (Review)
Review
BACKGROUND
The findings that α-crystallins are multi-functional proteins with diverse biological functions have generated considerable interest in understanding their role in health and disease. Recent studies have shown that chaperone peptides of α-crystallin could be delivered into cultured cells and in experimental animals with beneficial effects against protein aggregation, oxidation, inflammation and apoptosis.
SCOPE OF REVIEW
In this review, we will summarize the latest developments on the therapeutic potential of α-crystallins and their functional peptides.
MAJOR CONCLUSIONS
α-Crystallins and their functional peptides have shown significant favorable effects against several diseases. Their targeted delivery to tissues would be of great therapeutic benefit. However, α-crystallins can also function as disease-causing proteins. These seemingly contradictory functions must be carefully considered prior to their therapeutic use.
GENERAL SIGNIFICANCE
αA and αB-Crystallin are members of the small heat shock protein family. These proteins exhibit molecular chaperone and anti-apoptotic activities. The core crystallin domain within these proteins is largely responsible for these prosperities. Recent studies have identified peptides within the crystallin domain of both α- and αB-crystallins with remarkable chaperone and anti-apoptotic activities. Administration of α-crystallin or their functional peptides has shown substantial inhibition of pathologies in several diseases. However, α-crystallins have been shown to promote disease-causing pathways. These two sides of the proteins are discussed in this review. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.
Topics: Animals; Antioxidants; Brain Diseases; Eye Diseases; Molecular Chaperones; Peptides; Protein Aggregation, Pathological; alpha-Crystallins
PubMed: 25840354
DOI: 10.1016/j.bbagen.2015.03.012 -
Seminars in Cell & Developmental Biology Apr 2015Protein homeostasis (proteostasis) is essential for maintaining the functionality of the proteome. The disruption of proteostasis, due to genetic mutations or an... (Review)
Review
Protein homeostasis (proteostasis) is essential for maintaining the functionality of the proteome. The disruption of proteostasis, due to genetic mutations or an age-related decline, leads to aberrantly folded proteins that typically lose their function. The accumulation of misfolded and aggregated protein is also cytotoxic and has been implicated in the pathogenesis of neurodegenerative diseases. Neurons have developed an intrinsic protein quality control network, of which molecular chaperones are an essential component. Molecular chaperones function to promote efficient folding and target misfolded proteins for refolding or degradation. Increasing molecular chaperone expression can suppress protein aggregation and toxicity in numerous models of neurodegenerative disease; therefore, molecular chaperones are considered exciting therapeutic targets. Furthermore, mutations in several chaperones cause inherited neurodegenerative diseases. In this review, we focus on the importance of molecular chaperones in neurodegenerative diseases, and discuss the advances in understanding their protective mechanisms.
Topics: Animals; Heat-Shock Proteins; Humans; Molecular Chaperones; Neurodegenerative Diseases; Protein Aggregation, Pathological; Proteins
PubMed: 25770416
DOI: 10.1016/j.semcdb.2015.03.003 -
Cold Spring Harbor Perspectives in... Oct 2019Maintenance of a healthy and functional proteome in all cellular compartments is critical to cell and organismal homeostasis. Yet, our understanding of the proteostasis... (Review)
Review
Maintenance of a healthy and functional proteome in all cellular compartments is critical to cell and organismal homeostasis. Yet, our understanding of the proteostasis process within the nucleus is limited. Here, we discuss the identified roles of the major molecular chaperones Hsp90, Hsp70, and Hsp60 with client proteins working in diverse DNA-associated pathways. The unique challenges facing proteins in the nucleus are considered as well as the conserved features of the molecular chaperone system in facilitating DNA-linked processes. As nuclear protein inclusions are a common feature of protein-aggregation diseases (e.g., neurodegeneration), a better understanding of nuclear proteostasis is warranted.
Topics: Cell Nucleus; DNA; Humans; Molecular Chaperones; Nuclear Proteins
PubMed: 30745291
DOI: 10.1101/cshperspect.a034009