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Keywords = proteasome biogenesis

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22 pages, 3313 KiB  
Article
Transcriptome Analysis and CFEM Gene Overexpression in Metschnikowia bicuspidata Under Hemocyte and Iron Ion Stress
by Bingnan Zuo, Xiaodong Li, Ji Zhang, Bingyu Li, Na Sun and Fang Liang
Pathogens 2025, 14(7), 691; https://doi.org/10.3390/pathogens14070691 - 14 Jul 2025
Viewed by 349
Abstract
The “milky disease” in Chinese mitten crabs (Eriocheir sinensis), caused by Metschnikowia bicuspidata, poses significant threats to aquaculture, though its pathogenic mechanisms remain poorly understood. This study employs transcriptomic sequencing to analyze gene expression changes in Metschnikowia bicuspidata under hemocyte [...] Read more.
The “milky disease” in Chinese mitten crabs (Eriocheir sinensis), caused by Metschnikowia bicuspidata, poses significant threats to aquaculture, though its pathogenic mechanisms remain poorly understood. This study employs transcriptomic sequencing to analyze gene expression changes in Metschnikowia bicuspidata under hemocyte challenge, iron overload (1 mmol/mL), and combined stress, with functional validation through Common in Fungal Extracellular Membrane (CFEMgene) overexpression strains. Key findings reveal that (1) hemocyte challenge activated base excision repair (−log10[P] = 7.58) and ribosome biogenesis pathways, indicating fungal adaptation through DNA repair and enhanced protein synthesis to counter host immune attacks (e.g., ROS-mediated damage). (2) Iron overload induced glutathione metabolism and pentose phosphate pathway enrichment, demonstrating mitigation of ferroptosis through NADPH/GSH antioxidant systems and autophagy/proteasome coordination. (3) Under combined stress, ribosome biogenesis (−log10[P] = 1.3) and non-homologous end-joining pathways coordinated DNA repair with stress protein synthesis, complemented by vacuolar V-ATPase-mediated iron compartmentalization. (4) CFEM genes showed significant upregulation under hemocyte stress, with overexpression strains exhibiting enhanced biofilm formation (35% increased MTT cytotoxicity) and infectivity (40% higher infection rate), confirming CFEM domains mediate pathogenesis through iron homeostasis and virulence factor production. This work elucidates how M. bicuspidata employs metabolic reprogramming, oxidative stress responses, and CFEM-mediated iron regulation to establish infection, providing critical insights for developing targeted control strategies against milky disease. Full article
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26 pages, 5062 KiB  
Article
Expression Profiles of Housekeeping Genes and Tissue-Specific Genes in Different Tissues of Chinese Sturgeon (Acipenser sinensis)
by Yanping Li, Yunyun Lv, Peilin Cheng, Ying Jiang, Cao Deng, Yongming Wang, Zhengyong Wen, Jiang Xie, Jieming Chen, Qiong Shi and Hao Du
Animals 2024, 14(23), 3357; https://doi.org/10.3390/ani14233357 - 21 Nov 2024
Viewed by 1444
Abstract
The Chinese sturgeon (Acipenser sinensis) is an ancient, complex autooctoploid fish species that is currently facing conservation challenges throughout its distribution. To comprehensively characterize the expression profiles of genes and their associated biological functions across different tissues, we performed a transcriptome-scale [...] Read more.
The Chinese sturgeon (Acipenser sinensis) is an ancient, complex autooctoploid fish species that is currently facing conservation challenges throughout its distribution. To comprehensively characterize the expression profiles of genes and their associated biological functions across different tissues, we performed a transcriptome-scale gene expression analysis, focusing on housekeeping genes (HKGs), tissue-specific genes (TSGs), and co-expressed gene modules in various tissues. We collected eleven tissues to establish a transcriptomic repository, including data from Pacific Biosciences isoform sequencing (PacBio Iso-seq) and RNA sequencing (RNA-seq), and then obtained 25,434 full-length transcripts, with lengths from 307 to 9515 bp and an N50 of 3195 bp. Additionally, 20,887 transcripts were effectively identified and classified as known homologous genes. We also identified 787 HKGs, and the number of TSGs varied from 25 in the liver to 2073 in the brain. TSG functions were mainly enriched in certain signaling pathways involved in specific physiological processes, such as voltage-gated potassium channel activity, nervous system development, glial cell differentiation in the brain, and leukocyte transendothelial migration in the spleen and pronephros. Meanwhile, HKGs were highly enriched in some pathways involved in ribosome biogenesis, proteasome core complex, spliceosome activation, elongation factor activity, and translation initiation factor activity, which have been strongly implicated in fundamental biological tissue functions. We also predicted five modules, with eight hub genes in the brown module, most of which (such as rps3a, rps7, rps23, rpl11, rpl17, rpl27, and rpl28) were linked to ribosome biogenesis. Our results offer insights into ribosomal proteins that are indispensable in ribosome biogenesis and protein synthesis, which are crucial in various cell developmental processes and neural development of Chinese sturgeon. Overall, these findings will not only advance the understanding of fundamental biological functions in Chinese sturgeon but also supply a valuable genetic resource for characterizing this extremely important species. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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17 pages, 4098 KiB  
Article
Efficacy and Molecular Mechanisms of Nystatin Against Botrytis cinerea on Postharvest Table Grape
by Yingying Wu, Shen Zhang, Jingyi Wang, Fan He, Haocheng Wei, Dongxiao Chen and Ying Wang
Foods 2024, 13(22), 3624; https://doi.org/10.3390/foods13223624 - 13 Nov 2024
Cited by 1 | Viewed by 1592
Abstract
The primary cause of postharvest loss in table grape fruit is attributed to gray mold, which is caused by Botrytis cinerea. The present study confirmed the inhibitory effects of nystatin on the growth and development of B. cinerea, which led to [...] Read more.
The primary cause of postharvest loss in table grape fruit is attributed to gray mold, which is caused by Botrytis cinerea. The present study confirmed the inhibitory effects of nystatin on the growth and development of B. cinerea, which led to a remarkable reduction in the severity of gray mold on table grape fruits. Furthermore, the application of nystatin disrupted the membrane permeability of B. cinerea, causing increased cellular leakage and cell death. In addition, the transcriptome analysis showed that the application of nystatin effectively modulated the transcriptional profile of genes involved in ribosome and mitochondrion biogenesis, as well as oxidoreductase activity, thereby disrupting the homeostasis of cellular organelles. Moreover, the nystatin treatment down-regulated genes associated with membrane trafficking, protein degradation by the ubiquitin–proteasome system, and the autophagy process, ultimately attenuating the pathogenicity of B. cinerea. Collectively, nystatin can be considered a viable agent for managing gray mold on table grape fruit. Full article
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15 pages, 6587 KiB  
Article
Transcriptomic Characterization of Key Factors and Signaling Pathways for the Regeneration of Partially Hepatectomized Liver in Zebrafish
by Guili Song, Guohui Feng, Qing Li, Jinrong Peng, Wei Ge, Yong Long and Zongbin Cui
Int. J. Mol. Sci. 2024, 25(13), 7212; https://doi.org/10.3390/ijms25137212 - 29 Jun 2024
Viewed by 2102
Abstract
Liver regeneration induced by partial hepatectomy (PHx) has attracted intensive research interests due to the great significance for liver resection and transplantation. The zebrafish (Danio rerio) is an excellent model to study liver regeneration. In the fish subjected to PHx (the [...] Read more.
Liver regeneration induced by partial hepatectomy (PHx) has attracted intensive research interests due to the great significance for liver resection and transplantation. The zebrafish (Danio rerio) is an excellent model to study liver regeneration. In the fish subjected to PHx (the tip of the ventral lobe was resected), the lost liver mass could be fully regenerated in seven days. However, the regulatory mechanisms underlying the liver regeneration remain largely unknown. In this study, gene expression profiles during the regeneration of PHx-treated liver were explored by RNA sequencing (RNA-seq). The genes responsive to the injury of PHx treatment were identified and classified into different clusters based on the expression profiles. Representative gene ontology (GO) enrichments for the early responsive genes included hormone activity, ribosome biogenesis and rRNA processing, etc., while the late responsive genes were enriched in biological processes such as glutathione metabolic process, antioxidant activity and cellular detoxification. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments were also identified for the differentially expressed genes (DEGs) between the time-series samples and the sham controls. The proteasome was overrepresented by the up-regulated genes at all of the sampling time points. Inhibiting proteasome activity by the application of MG132 to the fish enhanced the expression of Pcna (proliferating cell nuclear antigen), an indicator of hepatocyte proliferation after PHx. Our data provide novel insights into the molecular mechanisms underlying the regeneration of PHx-treated liver. Full article
(This article belongs to the Special Issue Zebrafish as a Model in Human Disease: 3rd Edition)
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12 pages, 1893 KiB  
Review
Role of TFEB in Huntington’s Disease
by Javier Ojalvo-Pacheco, Sokhna M. S. Yakhine-Diop, José M. Fuentes, Marta Paredes-Barquero and Mireia Niso-Santano
Biology 2024, 13(4), 238; https://doi.org/10.3390/biology13040238 - 4 Apr 2024
Cited by 1 | Viewed by 3322
Abstract
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of the CAG trinucleotide repeat in exon 1 of the huntingtin (HTT) gene. This expansion leads to a polyglutamine (polyQ) tract at the N-terminal end of HTT, which reduces the [...] Read more.
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of the CAG trinucleotide repeat in exon 1 of the huntingtin (HTT) gene. This expansion leads to a polyglutamine (polyQ) tract at the N-terminal end of HTT, which reduces the solubility of the protein and promotes its accumulation. Inefficient clearance of mutant HTT (mHTT) by the proteasome or autophagy–lysosomal system leads to accumulation of oligomers and toxic protein aggregates in neurons, resulting in impaired proteolytic systems, transcriptional dysregulation, impaired axonal transport, mitochondrial dysfunction and cellular energy imbalance. Growing evidence suggests that the accumulation of mHTT aggregates and autophagic and/or lysosomal dysfunction are the major pathogenic mechanisms underlying HD. In this context, enhancing autophagy may be an effective therapeutic strategy to remove protein aggregates and improve cell function. Transcription factor EB (TFEB), a master transcriptional regulator of autophagy, controls the expression of genes critical for autophagosome formation, lysosomal biogenesis, lysosomal function and autophagic flux. Consequently, the induction of TFEB activity to promote intracellular clearance may be a therapeutic strategy for HD. However, while some studies have shown that overexpression of TFEB facilitates the clearance of mHTT aggregates and ameliorates the disease phenotype, others indicate such overexpression may lead to mHTT co-aggregation and worsen disease progression. Further studies are necessary to confirm whether TFEB modulation could be an effective therapeutic strategy against mHTT-mediated toxicity in different disease models. Full article
(This article belongs to the Special Issue Lysosomes and Diseases Associated with Its Dysfunction)
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30 pages, 6865 KiB  
Systematic Review
Oxidative Stress in Spinocerebellar Ataxia Type 3 and Its Attenuation by Herbal Remedies in Traditional Chinese Medicine: A Systematic Review
by Nur Shahirah Mohd Hisam and Kah Hui Wong
Antioxidants 2024, 13(3), 375; https://doi.org/10.3390/antiox13030375 - 19 Mar 2024
Cited by 3 | Viewed by 4786
Abstract
Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder that gives rise to motor incoordination and progressive functional disabilities. Although pharmacological interventions have revealed promising prospects in the management of SCA3, adverse effects may become unbearable. The use of herbal remedies [...] Read more.
Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder that gives rise to motor incoordination and progressive functional disabilities. Although pharmacological interventions have revealed promising prospects in the management of SCA3, adverse effects may become unbearable. The use of herbal remedies in traditional Chinese medicine (TCM) may serve as potential alternative medicines to delay the progression of the disease. This systematic review is intended to identify, appraise, and summarize the findings of studies pertaining to the therapeutic roles of herbal remedies in TCM targeting oxidative stress in the management of SCA3. A literature search for relevant articles published from 1 January 2013 to 30 June 2023 in three databases, namely PubMed, Web of Science, and Scopus, was carried out according to the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of ten preclinical studies met the inclusion criteria of the systematic review. We recognized the therapeutic potential of Brassica napus, Codonopsis pilosula, Curcuma sp., Gardenia jasminoides, Gastrodia elata, Ginkgo biloba, Glycyrrhiza inflata, Hericium erinaceus, Hyptis sp., Paeonia lactiflora, Panax ginseng, Poria cocos, Pueraria lobata, Rehmannia glutinosa, and Scrophularia ningpoensis. We identified the types of preclinical models expressing polyglutamine (polyQ) expanded mutant protein (mATXN3), inducers of oxidative stress that mimic the SCA3 pathogenesis, and effective doses of the herbal remedies. The modes of action contributing to the attenuation of oxidative stress are activation of antioxidant pathways, ubiquitin–proteasome system and autophagy, regulation of apoptosis, proinflammatory signaling pathway and chaperones, regulation of mitochondrial function and biogenesis, and restoration of neurotransmission and synaptic plasticity. In conclusion, herbal remedies in TCM may possibly delay the progression of SCA3, therefore providing justification for clinical trials. Full article
(This article belongs to the Special Issue Antioxidant Potential in Medicinal Plants)
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16 pages, 2746 KiB  
Article
Regulator of Ribosome Synthesis 1 (RRS1) Stabilizes GRP78 and Promotes Breast Cancer Progression
by Wenjing Sun, Junying Song, Qinglan Wu, Lin Deng, Tenglong Zhang, Li Zhang, Yanan Hua, Yi Cao and Lin Hou
Molecules 2024, 29(5), 1051; https://doi.org/10.3390/molecules29051051 - 28 Feb 2024
Cited by 2 | Viewed by 1960
Abstract
Regulator of ribosome synthesis 1 (RRS1), a crucial regulatory factor in ribosome biogenesis, exerts a remarkable impact on the progression of breast cancer (BC). However, the exact mechanisms and pathways have not yet been fully elucidated. To investigate the impact of RRS1 on [...] Read more.
Regulator of ribosome synthesis 1 (RRS1), a crucial regulatory factor in ribosome biogenesis, exerts a remarkable impact on the progression of breast cancer (BC). However, the exact mechanisms and pathways have not yet been fully elucidated. To investigate the impact of RRS1 on BC growth and metastasis, along with its underlying mechanisms. We discovered that RRS1 is overexpressed in BC tissues and cell lines. This study aims to regulate the level of RRS1 through lentiviral transfection technology to explore its potential function in BC cells. Knockdown of RRS1 resulted in the inhibition of cell proliferation, invasion, and migration, whereas overexpression had the opposite effects. We firstly identified the interaction between RRS1 and Glucose-Regulated Protein 78 (GRP78) using Co-immunoprecipitation (Co-IP) combined with mass spectrometry analysis, providing evidences of co-localization and positive regulation between RRS1 and GRP78. We observed that RRS1 inhibited the degradation of GRP78 through the ubiquitin–proteasome pathway, resulting in the stabilization of GRP78. In addition, our findings suggested that RRS1 promoted BC progression by activating the GRP78-mediated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. In conclusion, this newly discovered RRS1/GRP78 signaling axis provides a molecular and theoretical basis for further exploring the mechanisms of breast cancer invasion and metastasis. Full article
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37 pages, 24151 KiB  
Article
Nicotinamide Mononucleotide (NMN) Works in Type 2 Diabetes through Unexpected Effects in Adipose Tissue, Not by Mitochondrial Biogenesis
by Roua Gabriela Popescu, Anca Dinischiotu, Teodoru Soare, Ene Vlase and George Cătălin Marinescu
Int. J. Mol. Sci. 2024, 25(5), 2594; https://doi.org/10.3390/ijms25052594 - 23 Feb 2024
Cited by 2 | Viewed by 5092
Abstract
Nicotinamide mononucleotide (NMN) has emerged as a promising therapeutic intervention for age-related disorders, including type 2 diabetes. In this study, we confirmed the previously observed effects of NMN treatment on glucose uptake and investigated its underlying mechanisms in various tissues and cell lines. [...] Read more.
Nicotinamide mononucleotide (NMN) has emerged as a promising therapeutic intervention for age-related disorders, including type 2 diabetes. In this study, we confirmed the previously observed effects of NMN treatment on glucose uptake and investigated its underlying mechanisms in various tissues and cell lines. Through the most comprehensive proteomic analysis to date, we discovered a series of novel organ-specific effects responsible for glucose uptake as measured by the IPGTT: adipose tissue growing (suggested by increased protein synthesis and degradation and mTOR proliferation signaling upregulation). Notably, we observed the upregulation of thermogenic UCP1, promoting enhanced glucose conversion to heat in intermuscular adipose tissue while showing a surprising repressive effect on mitochondrial biogenesis in muscle and the brain. Additionally, liver and muscle cells displayed a unique response, characterized by spliceosome downregulation and concurrent upregulation of chaperones, proteasomes, and ribosomes, leading to mildly impaired and energy-inefficient protein synthesis machinery. Furthermore, our findings revealed remarkable metabolic rewiring in the brain. This involved increased production of ketone bodies, downregulation of mitochondrial OXPHOS and TCA cycle components, as well as the induction of well-known fasting-associated effects. Collectively, our data elucidate the multifaceted nature of NMN action, highlighting its organ-specific effects and their role in improving glucose uptake. These findings deepen our understanding of NMN’s therapeutic potential and pave the way for novel strategies in managing metabolic disorders. Full article
(This article belongs to the Special Issue Proteomics and Its Applications in Disease: 2nd Edition)
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21 pages, 1613 KiB  
Article
The Identification of Nuclear FMRP Isoform Iso6 Partners
by Nassim Ledoux, Emeline I. J. Lelong, Alexandre Simard, Samer Hussein, Pauline Adjibade, Jean-Philippe Lambert and Rachid Mazroui
Cells 2023, 12(24), 2807; https://doi.org/10.3390/cells12242807 - 9 Dec 2023
Cited by 3 | Viewed by 1666
Abstract
A deficiency of FMRP, a canonical RNA-binding protein, causes the development of Fragile X Syndrome (FXS), which is characterised by multiple phenotypes, including neurodevelopmental disorders, intellectual disability, and autism. Due to the alternative splicing of the encoding FMR1 gene, multiple FMRP isoforms are [...] Read more.
A deficiency of FMRP, a canonical RNA-binding protein, causes the development of Fragile X Syndrome (FXS), which is characterised by multiple phenotypes, including neurodevelopmental disorders, intellectual disability, and autism. Due to the alternative splicing of the encoding FMR1 gene, multiple FMRP isoforms are produced consisting of full-length predominantly cytoplasmic (i.e., iso1) isoforms involved in translation and truncated nuclear (i.e., iso6) isoforms with orphan functions. However, we recently implicated nuclear FMRP isoforms in DNA damage response, showing that they negatively regulate the accumulation of anaphase DNA genomic instability bridges. This finding provided evidence that the cytoplasmic and nuclear functions of FMRP are uncoupled played by respective cytoplasmic and nuclear isoforms, potentially involving specific interactions. While interaction partners of cytoplasmic FMRP have been reported, the identity of nuclear FMRP isoform partners remains to be established. Using affinity purification coupled with mass spectrometry, we mapped the nuclear interactome of the FMRP isoform iso6 in U2OS. In doing so, we found FMRP nuclear interaction partners to be involved in RNA processing, pre-mRNA splicing, ribosome biogenesis, DNA replication and damage response, chromatin remodeling and chromosome segregation. By comparing interactions between nuclear iso6 and cytoplasmic iso1, we report a set of partners that bind specifically to the nuclear isoforms, mainly proteins involved in DNA-associated processes and proteasomal proteins, which is consistent with our finding that proteasome targets the nuclear FMRP iso6. The specific interactions with the nuclear isoform 6 are regulated by replication stress, while those with the cytoplasmic isoform 1 are largely insensitive to such stress, further supporting a specific role of nuclear isoforms in DNA damage response induced by replicative stress, potentially regulated by the proteasome. Full article
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22 pages, 5096 KiB  
Article
Ubiquitination Is a Novel Post-Translational Modification of VMP1 in Autophagy of Human Tumor Cells
by Felipe J. Renna, Juliana H. Enriqué Steinberg, Claudio D. Gonzalez, Maria Manifava, Mariana S. Tadic, Tamara Orquera, Carolina V. Vecino, Alejandro Ropolo, Daniele Guardavaccaro, Mario Rossi, Nicholas T. Ktistakis and Maria I. Vaccaro
Int. J. Mol. Sci. 2023, 24(16), 12981; https://doi.org/10.3390/ijms241612981 - 19 Aug 2023
Cited by 8 | Viewed by 3145
Abstract
Autophagy is a tightly regulated catabolic process involved in the degradation and recycling of proteins and organelles. Ubiquitination plays an important role in the regulation of autophagy. Vacuole Membrane Protein 1 (VMP1) is an essential autophagy protein. The expression of VMP1 in pancreatic [...] Read more.
Autophagy is a tightly regulated catabolic process involved in the degradation and recycling of proteins and organelles. Ubiquitination plays an important role in the regulation of autophagy. Vacuole Membrane Protein 1 (VMP1) is an essential autophagy protein. The expression of VMP1 in pancreatic cancer stem cells carrying the activated Kirsten rat sarcoma viral oncogene homolog (KRAS) triggers autophagy and enables therapy resistance. Using biochemical and cellular approaches, we identified ubiquitination as a post-translational modification of VMP1 from the initial steps in autophagosome biogenesis. VMP1 remains ubiquitinated as part of the autophagosome membrane throughout autophagic flux until autolysosome formation. However, VMP1 is not degraded by autophagy, nor by the ubiquitin–proteasomal system. Mass spectrometry and immunoprecipitation showed that the cell division cycle protein cdt2 (Cdt2), the substrate recognition subunit of the E3 ligase complex associated with cancer, cullin–RING ubiquitin ligase complex 4 (CRL4), is a novel interactor of VMP1 and is involved in VMP1 ubiquitination. VMP1 ubiquitination decreases under the CRL inhibitor MLN4924 and increases with Cdt2 overexpression. Moreover, VMP1 recruitment and autophagosome formation is significantly affected by CRL inhibition. Our results indicate that ubiquitination is a novel post-translational modification of VMP1 during autophagy in human tumor cells. VMP1 ubiquitination may be of clinical relevance in tumor-cell-therapy resistance. Full article
(This article belongs to the Special Issue Molecular Research on Autophagy)
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21 pages, 4395 KiB  
Review
Wiggle and Shake: Managing and Exploiting Conformational Dynamics during Proteasome Biogenesis
by Daniel Betancourt, Tomiwa Lawal and Robert J. Tomko
Biomolecules 2023, 13(8), 1223; https://doi.org/10.3390/biom13081223 - 6 Aug 2023
Cited by 1 | Viewed by 2482
Abstract
The 26S proteasome is the largest and most complicated protease known, and changes to proteasome assembly or function contribute to numerous human diseases. Assembly of the 26S proteasome from its ~66 individual polypeptide subunits is a highly orchestrated process requiring the concerted actions [...] Read more.
The 26S proteasome is the largest and most complicated protease known, and changes to proteasome assembly or function contribute to numerous human diseases. Assembly of the 26S proteasome from its ~66 individual polypeptide subunits is a highly orchestrated process requiring the concerted actions of both intrinsic elements of proteasome subunits, as well as assistance by extrinsic, dedicated proteasome assembly chaperones. With the advent of near-atomic resolution cryo-electron microscopy, it has become evident that the proteasome is a highly dynamic machine, undergoing numerous conformational changes in response to ligand binding and during the proteolytic cycle. In contrast, an appreciation of the role of conformational dynamics during the biogenesis of the proteasome has only recently begun to emerge. Herein, we review our current knowledge of proteasome assembly, with a particular focus on how conformational dynamics guide particular proteasome biogenesis events. Furthermore, we highlight key emerging questions in this rapidly expanding area. Full article
(This article belongs to the Special Issue Allosteric Regulation in Ubiquitin Proteasome System)
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20 pages, 7156 KiB  
Article
Transcriptome-Based Analysis of the Liver Response Mechanism of Black Porgy (Acanthopagrus schlegelii) to Stocking Density
by Tangjian Zhou, Chaofeng Jia, Qian Meng, Dafeng Xu, Zhiwei Zhang, Fei Zhu, Yonglei Zhao, Ruijian Sun, Yunxia Yang and Shuyin Chen
Fishes 2023, 8(7), 356; https://doi.org/10.3390/fishes8070356 - 8 Jul 2023
Cited by 4 | Viewed by 2103
Abstract
Long-term high stocking density often brings negative effects such as decreased body weight, decreased immunity, and increased mortality to cultured fish, while the effects of short-term stocking are relatively less studied. In this experiment, we characterized spatial and temporal gene expression in black [...] Read more.
Long-term high stocking density often brings negative effects such as decreased body weight, decreased immunity, and increased mortality to cultured fish, while the effects of short-term stocking are relatively less studied. In this experiment, we characterized spatial and temporal gene expression in black porgy (Acanthopagrus schlegelii) liver by establishing two stocking density groups—high (H: 26.5 kg/m3) and low (L: 2.95 kg/m3)—and conducting transcriptome sequencing before collecting liver samples at two time points: 6 h (AL and AH) and 60 d (CL and CH) into the culture trial. There were 648 and 550 differentially expressed genes (DEGs) in the AL-vs-AH and CL-vs-CH groups, respectively. The DEGs in the AL-vs-AH group were significantly enriched in steroid biosynthesis, terpenoid backbone biosynthesis, the PPAR signaling pathway, proteasome, aminoacyl-tRNA biosynthesis, and ribosome biogenesis in eukaryotes. The DEGs in the CL-vs-CH group were more significantly enriched in lipid metabolism-related pathways, such as the PPAR signaling pathway, fatty acid metabolism, and cholesterol metabolism. In addition, immune-related pathways such as the phagosome and complement and coagulation cascades were also enriched in the CL-vs-CH group. The expression changes concerning the DEGs in each group were further analyzed. The DEGs related to steroid synthesis, protein synthesis, and the degradation pathways were down-regulated, but immune-related genes were generally up-regulated in the AH group. The DEGs related to lipid synthesis were significantly up-regulated in the CH group, but the DEGs related to lipid consumption and utilization were down-regulated. The expression of immune-related DEGs was also negatively affected in the CH group. These results suggest that acute and chronic crowding stress affects lipid metabolism and immune regulation in the liver of black porgy. Acute stress particularly affected hepatic protein metabolism, while chronic stress showed more effects on hepatic lipid metabolism. The results of this study provide a theoretical basis for understanding the effects of high stocking densities upon black porgy and may also provide a reference for crowding stress regulation studies in other fish species. Full article
(This article belongs to the Section Genetics and Biotechnology)
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13 pages, 2408 KiB  
Article
Ribosome Biogenesis Regulator 1 Homolog (RRS1) Promotes Cisplatin Resistance by Regulating AEG-1 Abundance in Breast Cancer Cells
by Junying Song, Cuixiu Peng, Runze Wang, Yanan Hua, Qinglan Wu, Lin Deng, Yi Cao, Li Zhang and Lin Hou
Molecules 2023, 28(7), 2939; https://doi.org/10.3390/molecules28072939 - 25 Mar 2023
Cited by 5 | Viewed by 2431
Abstract
Many ribosomal proteins are highly expressed in tumors and are closely related to their diagnosis, prognosis and pathological characteristics. However, few studies are available on the correlation between ribosomal proteins and chemoresistance. RRS1 (human regulator of ribosome synthesis 1), a critical nuclear protein [...] Read more.
Many ribosomal proteins are highly expressed in tumors and are closely related to their diagnosis, prognosis and pathological characteristics. However, few studies are available on the correlation between ribosomal proteins and chemoresistance. RRS1 (human regulator of ribosome synthesis 1), a critical nuclear protein involved in ribosome biogenesis, also plays a key role in the genesis and development of breast cancer by protecting cancer cells from apoptosis. Given that apoptosis resistance is one of the causes of the cisplatin resistance of tumor cells, our aim was to determine the relationship between RRS1 and cisplatin resistance in breast cancer cells. Here, we report that RRS1 is associated with cisplatin resistance in breast cancer cells. RRS1 silencing increased the sensitivity of MCF-7/DDP cells to cisplatin and inhibited cancer cell proliferation by blocking cell cycle distribution and enhancing apoptosis. AEG-1 (astrocyte elevated gene-1) promotes drug resistance by interfering with the ubiquitination and proteasomal degradation of MDR1 (multidrug resistance gene 1), thereby enhancing drug efflux. We found that RRS1 binds to and stabilizes AEG-1 by inhibiting ubiquitination and subsequent proteasomal degradation, which then promotes drug efflux by upregulating MDR1. Furthermore, RRS1 also induces apoptosis resistance in breast cancer cells through the ERK/Bcl-2/BAX signaling pathway. Our study is the first to show that RRS1 sensitizes breast cancer cells to cisplatin by binding to AEG-1, and it provides a theoretical basis to improve the efficacy of cisplatin-based chemotherapy. Full article
(This article belongs to the Special Issue Functional Proteomics in Cell Biology and Beyond)
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18 pages, 3948 KiB  
Article
Hsp70 and Hsp110 Chaperones Promote Early Steps of Proteasome Assembly
by Ana C. Matias, Joao Matos, R. Jürgen Dohmen and Paula C. Ramos
Biomolecules 2023, 13(1), 11; https://doi.org/10.3390/biom13010011 - 21 Dec 2022
Cited by 6 | Viewed by 2400
Abstract
Whereas assembly of the 20S proteasome core particle (CP) in prokaryotes apparently occurs spontaneously, the efficiency of this process in eukaryotes relies on the dedicated assembly chaperones Ump1, Pba1-Pba2, and Pba3-Pba4. For mammals, it was reported that CP assembly initiates with formation of [...] Read more.
Whereas assembly of the 20S proteasome core particle (CP) in prokaryotes apparently occurs spontaneously, the efficiency of this process in eukaryotes relies on the dedicated assembly chaperones Ump1, Pba1-Pba2, and Pba3-Pba4. For mammals, it was reported that CP assembly initiates with formation of a complete α-ring that functions as a template for β subunit incorporation. By contrast, we were not able to detect a ring composed only of a complete set of α subunits in S. cerevisiae. Instead, we found that the CP subunits α1, α2, and α4 each form independent small complexes. Purification of such complexes containing α4 revealed the presence of chaperones of the Hsp70/Ssa and Hsp110/Sse families. Consistently, certain small complexes containing α1, α2, and α4 were not formed in strains lacking these chaperones. Deletion of the SSE1 gene in combination with deletions of PRE9 (α3), PBA3, or UMP1 genes resulted in severe synthetic growth defects, high levels of ubiquitin-conjugates, and an accumulation of distinct small complexes with α subunits. Our study shows that Hsp70 and Hsp110 chaperones cooperate to promote the folding of individual α subunits and/or their assembly with other CP subunits, Ump1, and Pba1-Pba4 in subsequent steps. Full article
(This article belongs to the Collection Feature Papers in Biochemistry)
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23 pages, 5011 KiB  
Article
The Dynamics of Cryptococcus neoformans Cell and Transcriptional Remodeling during Infection
by Gustavo J. C. Freitas, Ludmila Gouveia-Eufrasio, Eluzia C. P. Emidio, Hellem C. S. Carneiro, Ludmila de Matos Baltazar, Marliete C. Costa, Susana Frases, Glauber R. de Sousa Araújo, Tatiane A. Paixão, Brunno G. Sossai, Melissa Caza, James W. Kronstad, Nalu T. A. Peres and Daniel A. Santos
Cells 2022, 11(23), 3896; https://doi.org/10.3390/cells11233896 - 2 Dec 2022
Cited by 10 | Viewed by 3328
Abstract
The phenotypic plasticity of Cryptococcus neoformans is widely studied and demonstrated in vitro, but its influence on pathogenicity remains unclear. In this study, we investigated the dynamics of cryptococcal cell and transcriptional remodeling during pulmonary infection in a murine model. We showed that in [...] Read more.
The phenotypic plasticity of Cryptococcus neoformans is widely studied and demonstrated in vitro, but its influence on pathogenicity remains unclear. In this study, we investigated the dynamics of cryptococcal cell and transcriptional remodeling during pulmonary infection in a murine model. We showed that in Cryptococcus neoformans, cell size reduction (cell body ≤ 3 µm) is important for initial adaptation during infection. This change was associated with reproductive fitness and tissue invasion. Subsequently, the fungus develops mechanisms aimed at resistance to the host’s immune response, which is determinant for virulence. We investigated the transcriptional changes involved in this cellular remodeling and found an upregulation of transcripts related to ribosome biogenesis at the beginning (6 h) of infection and a later (10 days) upregulation of transcripts involved in the inositol pathway, energy production, and the proteasome. Consistent with a role for the proteasome, we found that its inhibition delayed cell remodeling during infection with the H99 strain. Altogether, these results further our understanding of the infection biology of C. neoformans and provide perspectives to support therapeutic and diagnostic targets for cryptococcosis. Full article
(This article belongs to the Collection Feature Papers in Plant, Algae and Fungi Cell Biology)
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