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Sub-cellular Biochemistry 2023Molecular chaperones and their associated co-chaperones are essential in health and disease as they are key facilitators of protein-folding, quality control and... (Review)
Review
Molecular chaperones and their associated co-chaperones are essential in health and disease as they are key facilitators of protein-folding, quality control and function. In particular, the heat-shock protein (HSP) 70 and HSP90 molecular chaperone networks have been associated with neurodegenerative diseases caused by aberrant protein-folding. The pathogenesis of these disorders usually includes the formation of deposits of misfolded, aggregated protein. HSP70 and HSP90, plus their co-chaperones, have been recognised as potent modulators of misfolded protein toxicity, inclusion formation and cell survival in cellular and animal models of neurodegenerative disease. Moreover, these chaperone machines function not only in folding but also in proteasome-mediated degradation of neurodegenerative disease proteins. This chapter gives an overview of the HSP70 and HSP90 chaperones, and their respective regulatory co-chaperones, and explores how the HSP70 and HSP90 chaperone systems form a larger functional network and its relevance to counteracting neurodegenerative disease associated with misfolded proteins and disruption of proteostasis.
Topics: Animals; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Molecular Chaperones; Neurodegenerative Diseases; Protein Folding
PubMed: 36520314
DOI: 10.1007/978-3-031-14740-1_13 -
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 -
Cell Stress & Chaperones Jun 2024More than 99% of the mitochondrial proteome is encoded by the nucleus and requires refolding following import. Therefore, mitochondrial proteins require the coordinated... (Review)
Review
More than 99% of the mitochondrial proteome is encoded by the nucleus and requires refolding following import. Therefore, mitochondrial proteins require the coordinated action of molecular chaperones for their folding and activation. Several heat shock protein (Hsp) molecular chaperones, including members of the Hsp27, Hsp40/70, and Hsp90 families, as well as the chaperonin complex Hsp60/10 have an established role in mitochondrial protein import and folding. The "Chaperone Code" describes the regulation of chaperone activity by dynamic post-translational modifications; however, little is known about the post-translational regulation of mitochondrial chaperones. Dissecting the regulation of chaperone function is essential for understanding their differential regulation in pathogenic conditions and the potential development of efficacious therapeutic strategies. Here, we summarize the recent literature on post-translational regulation of mitochondrial chaperones, the consequences for mitochondrial function, and potential implications for disease.
Topics: Humans; Mitochondria; Molecular Chaperones; Mitochondrial Proteins; Animals; Protein Processing, Post-Translational; Heat-Shock Proteins; Protein Folding
PubMed: 38763405
DOI: 10.1016/j.cstres.2024.05.002 -
Cold Spring Harbor Perspectives in... Mar 2023The endoplasmic reticulum (ER)-localized Hsp70 chaperone, BiP, undergoes a rapid, reversible and inactivating post-translational modification. This covalent modification... (Review)
Review
The endoplasmic reticulum (ER)-localized Hsp70 chaperone, BiP, undergoes a rapid, reversible and inactivating post-translational modification. This covalent modification complements the slower, conventional unfolded protein response (UPR) in matching the supply of active Hsp70 chaperone to the protein folding demand within the ER lumen. Long believed to be ADP-ribosylation, we now know this modification to be AMPylation (adenylylation) of BiP's threonine 518. Here, we review the discovery of the responsible enzyme (the Fic domain-containing protein FICD), the structural and biochemical basis of the inactivating modification and the discovery of FICD's dual role as the enzyme that both AMPylates and deAMPylates BiP. The structural basis of BiP recognition by FICD and recent in vitro insights into oligomeric state-mediated regulation of FICD's antagonistic enzymatic activities are also reviewed, the latter in the context of how such a regulatory system may arise in cells. Last, we consider the physiological significance of BiP AMPylation and speculate on the fitness benefits of this metazoan-specific adaptation.
Topics: Animals; Heat-Shock Proteins; Endoplasmic Reticulum; Endoplasmic Reticulum Chaperone BiP; Unfolded Protein Response; Molecular Chaperones; Protein Folding; Homeostasis
PubMed: 36041787
DOI: 10.1101/cshperspect.a041265