المؤلفون: Fujita, Yu, Tinoco, Roberto, Li, Yan, Senft, Daniela, Ronai, Ze'ev A

المصدر: Trends in Molecular Medicine. 25(5)

مصطلحات موضوعية: Autoimmune Disease, Biotechnology, Inflammatory and immune system, Animals, Autoimmunity, Biomarkers, Tumor, Humans, Immune Tolerance, Immunity, Immunologic Surveillance, Immunomodulation, Immunotherapy, Lymphocyte Activation, Neoplasms, Signal Transduction, T-Lymphocytes, Tumor Escape, Ubiquitin, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, Ubiquitination, E3 ubiquitin ligase, antitumor immunity, autoimmunity, immune checkpoint, Biological Sciences, Medical and Health Sciences, Immunology

الوصف: Considerable progress has been made in understanding the contribution of E3 ubiquitin ligases to health and disease, including the pathogenesis of immunological disorders. Ubiquitin ligases exert exquisite spatial and temporal control over protein stability and function, and are thus crucial for the regulation of both innate and adaptive immunity. Given that immune responses can be both detrimental (autoimmunity) and beneficial (antitumor immunity), it is vital to understand how ubiquitin ligases maintain immunological homeostasis. Such knowledge could reveal novel mechanisms underlying immune regulation and identify new therapeutic approaches to enhance antitumor immunity and safeguard against autoimmunity.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6j2846dkTest

المؤلفون: Garranzo-Asensio, M., Segundo-Acosta, P. S., Martínez-Useros, J., Montero-Calle, A., Fernández-Aceñero, M. J., Månberg, Anna, 1985, Pelaez-Garcia, A., Villalba, M., Rabano, A., Nilsson, P., Barderas, R.

المصدر: Oncotarget. 9(13):10847-10867

مصطلحات موضوعية: Alzheimer's disease, Gerotarget/Aging, Neurodegeneration, Protein/antibody microarrays, Proteomics, alpha2 glycoprotein, Bruton tyrosine kinase, CD36 antigen, chromogranin A, ferritin, ferritin light chain, furin, galectin 3, galectin 3 binding protein, growth arrest and DNA damage inducible protein 153, Layilin, mannose binding lectin 2, messenger RNA, MHC class I polypeptide related sequence B, protein kinase C, somatostatin receptor 2, stratum corneum chymotryptic enzyme, stress activated protein kinase 1, synexin, tau protein, ubiquitin protein ligase E3, ubiquitin protein ligase TOPORS, unclassified drug, X linked inhibitor of apoptosis, zinc alpha 2 glycoprotein, aged, Alzheimer disease, Article, BTK gene, clinical article, controlled study, down regulation, female, fluorescence in situ hybridization, frontotemporal dementia, gene, high throughput sequencing, human, human tissue, immunohistochemistry, KLK7 gene, male, mRNA expression level, multiinfarct dementia, NELL2 gene, prefrontal cortex, protein analysis, protein expression, signal transduction, tissue microarray, upregulation, very elderly, Western blotting

الوصف: Alzheimer's disease (AD) is the most common form of dementia in developed countries. A better understanding of the events taking place at the molecular level would help to identify novel protein alterations, which might be used in diagnosis or for treatment development. In this study, we have performed the high-throughput analysis of 706 molecules mostly implicated in cell-cell communication and cell signaling processes by using two antibody microarray platforms. We screened three AD pathological groups -each one containing four pooled samples- from Braak stages IV, V and VI, and three control groups from two healthy subjects, five frontotemporal and two vascular dementia patients onto Panorama and L-Series antibody microarrays to identify AD-specific alterations not common to other dementias. Forty altered proteins between control and AD groups were detected, and validated by i) meta-analysis of mRNA alterations, ii) WB, and iii) FISH and IHC using an AD-specific tissue microarray containing 44 samples from AD patients at different Braak stages, and frontotemporal and vascular dementia patients and healthy individuals as controls. We identified altered proteins in AD not common to other dementias like the E3 ubiquitin-protein ligase TOPORS, Layilin and MICB, and validated the association to AD of the previously controverted proteins DDIT3 and the E3 ubiquitin-protein ligase XIAP. These altered proteins constitute interesting targets for further immunological analyses using sera, plasma and CSF to identify AD blood- or cerebrospinal fluidbiomarkers and to perform functional analysis to determine their specific role in AD, and their usefulness as potential therapeutic targets of intervention.

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-282708Test
https://doi.org/10.18632/oncotarget.24303Test

المؤلفون: Alvaro, Christopher G, Aindow, Ann, Thorner, Jeremy

المصدر: Genetics. 203(1)

مصطلحات موضوعية: Biochemistry and Cell Biology, Biological Sciences, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Adaptation, Biological, Calcineurin, Down-Regulation, Endosomal Sorting Complexes Required for Transport, Glycogen Synthase Kinase 3, Membrane Proteins, Phosphorylation, Protein Binding, Protein Interaction Domains and Motifs, Protein Serine-Threonine Kinases, Receptors, Mating Factor, Reproduction, Asexual, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Ubiquitin-Protein Ligase Complexes, mating pheromone response, adaptation, desensitization, down-regulation, endocytosis, Genetics, Developmental Biology, Biochemistry and cell biology

الوصف: G-protein-coupled receptors (GPCRs) are integral membrane proteins that initiate stimulus-dependent activation of cognate heterotrimeric G-proteins, triggering ensuing downstream cellular responses. Tight regulation of GPCR-evoked pathways is required because prolonged stimulation can be detrimental to an organism. Ste2, a GPCR in Saccharomyces cerevisiae that mediates response of MATa haploids to the peptide mating pheromone α-factor, is down-regulated by both constitutive and agonist-induced endocytosis. Efficient agonist-stimulated internalization of Ste2 requires its association with an adaptor protein, the α-arrestin Rod1/Art4, which recruits the HECT-domain ubiquitin ligase Rsp5, allowing for ubiquitinylation of the C-terminal tail of the receptor and its engagement by the clathrin-dependent endocytic machinery. We previously showed that dephosphorylation of Rod1 by calcineurin (phosphoprotein phosphatase 2B) is required for optimal Rod1 function in Ste2 down-regulation. We show here that negative regulation of Rod1 by phosphorylation is mediated by two distinct stress-activated protein kinases, Snf1/AMPK and Ypk1/SGK1, and demonstrate both in vitro and in vivo that this phospho-regulation impedes the ability of Rod1 to promote mating pathway desensitization. These studies also revealed that, in the absence of its phosphorylation, Rod1 can promote adaptation independently of Rsp5-mediated receptor ubiquitinylation, consistent with recent evidence that α-arrestins can contribute to cargo recognition by both clathrin-dependent and clathrin-independent mechanisms. However, in cells lacking a component (formin Bni1) required for clathrin-independent entry, Rod1 derivatives that are largely unphosphorylated and unable to associate with Rsp5 still promote efficient adaptation, indicating a third mechanism by which this α-arrestin promotes desensitization of the pheromone-response pathway.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/3k9693wgTest

المؤلفون: Hodge, Curtis D, Ismail, Ismail H, Edwards, Ross A, Hura, Greg L, Xiao, Andrew T, Tainer, John A, Hendzel, Michael J, Glover, JN Mark

المصدر: Journal of Biological Chemistry. 291(18)

مصطلحات موضوعية: Biochemistry and Cell Biology, Biological Sciences, Cancer, Genetics, Generic health relevance, Animals, BRCA1 Protein, Crystallography, X-Ray, DNA Breaks, Double-Stranded, Mice, Protein Structure, Quaternary, Signal Transduction, Tumor Suppressor Proteins, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitination, 53BP1, BRCA1, DNA damage response, E3 ubiquitin-protein ligase RNF8, RNF168, Ubc13, cell biology, ubiquitylation, x-ray crystallography, x-ray scattering, Chemical Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences

الوصف: DNA double strand break (DSB) responses depend on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 plus E2 ubiquitin-conjugating enzyme Ubc13 to specifically generate histone Lys-63-linked ubiquitin chains in DSB signaling. Here, we defined the activated RNF8-Ubc13∼ubiquitin complex by x-ray crystallography and its functional solution conformations by x-ray scattering, as tested by separation-of-function mutations imaged in cells by immunofluorescence. The collective results show that the RING E3 RNF8 targets E2 Ubc13 to DSB sites and plays a critical role in damage signaling by stimulating polyubiquitination through modulating conformations of ubiquitin covalently linked to the Ubc13 active site. Structure-guided separation-of-function mutations show that the RNF8 E2 stimulating activity is essential for DSB signaling in mammalian cells and is necessary for downstream recruitment of 53BP1 and BRCA1. Chromatin-targeted RNF168 rescues 53BP1 recruitment involved in non-homologous end joining but not BRCA1 recruitment for homologous recombination. These findings suggest an allosteric approach to targeting the ubiquitin-docking cleft at the E2-E3 interface for possible interventions in cancer and chronic inflammation, and moreover, they establish an independent RNF8 role in BRCA1 recruitment.

الوصول الحر: https://escholarship.org/uc/item/3sg7k2t8Test

المؤلفون: Alvaro, Christopher G, O'Donnell, Allyson F, Prosser, Derek C, Augustine, Andrew A, Goldman, Aaron, Brodsky, Jeffrey L, Cyert, Martha S, Wendland, Beverly, Thorner, Jeremy

المصدر: Molecular and Cellular Biology. 34(14)

مصطلحات موضوعية: 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Arrestins, Calcineurin, Carrier Proteins, Cell Cycle, Endosomal Sorting Complexes Required for Transport, Gene Expression Regulation, Fungal, Mating Factor, Membrane Proteins, Peptides, Pheromones, Phosphorylation, Receptors, Mating Factor, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Ubiquitin-Protein Ligase Complexes, Ubiquitination, Biological Sciences, Medical and Health Sciences, Developmental Biology

الوصف: G-protein-coupled receptors (GPCRs) are integral membrane proteins that initiate responses to extracellular stimuli by mediating ligand-dependent activation of cognate heterotrimeric G proteins. In yeast, occupancy of GPCR Ste2 by peptide pheromone α-factor initiates signaling by releasing a stimulatory Gβγ complex (Ste4-Ste18) from its inhibitory Gα subunit (Gpa1). Prolonged pathway stimulation is detrimental, and feedback mechanisms have evolved that act at the receptor level to limit the duration of signaling and stimulate recovery from pheromone-induced G1 arrest, including upregulation of the expression of an α-factor-degrading protease (Bar1), a regulator of G-protein signaling protein (Sst2) that stimulates Gpa1-GTP hydrolysis, and Gpa1 itself. Ste2 is also downregulated by endocytosis, both constitutive and ligand induced. Ste2 internalization requires its phosphorylation and subsequent ubiquitinylation by membrane-localized protein kinases (Yck1 and Yck2) and a ubiquitin ligase (Rsp5). Here, we demonstrate that three different members of the α-arrestin family (Ldb19/Art1, Rod1/Art4, and Rog3/Art7) contribute to Ste2 desensitization and internalization, and they do so by discrete mechanisms. We provide genetic and biochemical evidence that Ldb19 and Rod1 recruit Rsp5 to Ste2 via PPXY motifs in their C-terminal regions; in contrast, the arrestin fold domain at the N terminus of Rog3 is sufficient to promote adaptation. Finally, we show that Rod1 function requires calcineurin-dependent dephosphorylation.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5cj6p3gpTest

المؤلفون: Sirisaengtaksin, Natalie, Gireud, Monica, Yan, Qing, Kubota, Yoshihisa, Meza, Denisse, Waymire, Jack C, Zage, Peter E, Bean, Andrew J

المصدر: Journal of Biological Chemistry. 289(5)

مصطلحات موضوعية: Biochemistry and Cell Biology, Biological Sciences, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Cell Membrane, Endopeptidases, Endosomal Sorting Complexes Required for Transport, Endosomes, ErbB Receptors, HeLa Cells, Humans, Membrane Proteins, Phosphoproteins, Protein Interaction Domains and Motifs, Protein Structure, Tertiary, Protein Transport, Proteolysis, Signal Transduction, Tumor Suppressor Proteins, Ubiquitin Thiolesterase, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, Ubiquitination, Deubiquitination, E3 Ubiquitin Ligase, Endocytosis, Protein Sorting, ESCRT, USP8, Hela Cells, Chemical Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences

الوصف: The signaling of plasma membrane proteins is tuned by internalization and sorting in the endocytic pathway prior to recycling or degradation in lysosomes. Ubiquitin modification allows recognition and association of cargo with endosomally associated protein complexes, enabling sorting of proteins to be degraded from those to be recycled. The mechanism that provides coordination between the cellular machineries that mediate ubiquitination and endosomal sorting is unknown. We report that the ubiquitin ligase UBE4B is recruited to endosomes in response to epidermal growth factor receptor (EGFR) activation by binding to Hrs, a key component of endosomal sorting complex required for transport (ESCRT) 0. We identify the EGFR as a substrate for UBE4B, establish UBE4B as a regulator of EGFR degradation, and describe a mechanism by which UBE4B regulates endosomal sorting, affecting cellular levels of the EGFR and its downstream signaling. We propose a model in which the coordinated action of UBE4B, ESCRT-0, and the deubiquitinating enzyme USP8 enable the endosomal sorting and lysosomal degradation of the EGFR.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/43p465fqTest

المؤلفون: Chun Liang Chen, Tim H M Huang, Xiang Gu, Thu Minh Duong, Marieke Burleson, Haojie Huang, Yuqian Yan, Yi Zou, Michael A. Liss, Thomas G. Boyer, Lu-Zhe Sun, P. Renee Yew, Acarizia Easley, Addanki P. Kumar, Debodipta Das, Janice Jianhong Deng, Yi Chen, Tai Qin, Roble Bedolla

المصدر: Mol Cancer Res

مصطلحات موضوعية: Male, Cancer Research, animal structures, medicine.drug_class, Nerve Tissue Proteins, SPOP, Article, Mice, Prostate cancer, Castration Resistance, Zinc Finger Protein Gli3, Cell Line, Tumor, medicine, Animals, Humans, Sonic hedgehog, Molecular Biology, biology, business.industry, Nuclear Proteins, Ubiquitin-Protein Ligase Complexes, Gene signature, Androgen, medicine.disease, Repressor Proteins, Androgen receptor, Prostatic Neoplasms, Castration-Resistant, Oncology, Receptors, Androgen, Mutation, embryonic structures, biology.protein, Cancer research, Signal transduction, business

الوصف: Although the Sonic hedgehog (SHH) signaling pathway has been implicated in promoting malignant phenotypes of prostate cancer, details on how it is activated and exerts its oncogenic role during prostate cancer development and progression is less clear. Here, we show that GLI3, a key SHH pathway effector, is transcriptionally upregulated during androgen deprivation and posttranslationally stabilized in prostate cancer cells by mutation of speckle-type POZ protein (SPOP). GLI3 is a substrate of SPOP-mediated proteasomal degradation in prostate cancer cells and prostate cancer driver mutations in SPOP abrogate GLI3 degradation. Functionally, GLI3 is necessary and sufficient for the growth and migration of androgen receptor (AR)–positive prostate cancer cells, particularly under androgen-depleted conditions. Importantly, we demonstrate that GLI3 physically interacts and functionally cooperates with AR to enrich an AR-dependent gene expression program leading to castration-resistant growth of xenografted prostate tumors. Finally, we identify an AR/GLI3 coregulated gene signature that is highly correlated with castration-resistant metastatic prostate cancer and predictive of disease recurrence. Together, these findings reveal that hyperactivated GLI3 promotes castration-resistant growth of prostate cancer and provide a rationale for therapeutic targeting of GLI3 in patients with castration-resistant prostate cancer (CRPC). Implications: We describe two clinically relevant mechanisms leading to hyperactivated GLI3 signaling and enhanced AR/GLI3 cross-talk, suggesting that GLI3-specific inhibitors might prove effective to block prostate cancer development or delay CRPC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::52ce740d5638259a84c2bc8945818a08Test
https://doi.org/10.1158/1541-7786.mcr-21-0108Test

المؤلفون: Mingqi Li, Ling Li, Sarah Asemota, David Kakhniashvili, Ramesh Narayanan, Xusheng Wang, Francesca-Fang Liao

المصدر: Proceedings of the National Academy of Sciences. 119

مصطلحات موضوعية: Inflammation, Multidisciplinary, Deubiquitinating Enzymes, Drug Resistance, Neoplasm, Endopeptidases, Necroptosis, NF-kappa B, Ubiquitination, Humans, Ubiquitin-Protein Ligase Complexes, Protein Multimerization, DNA Damage, Signal Transduction

الوصف: Targeting nuclear factor-kappa B (NF-κB) represents a highly viable strategy against chemoresistance in cancers as well as cell death. Ubiquitination, including linear ubiquitination mediated by the linear ubiquitin chain assembly complex (LUBAC), is emerging as a crucial mechanism of overactivated NF-κB signaling. Ovarian tumor family deubiquitinase OTULIN is the only linear linkage–specific deubiquitinase; however, the molecular mechanisms of how it counteracts LUBAC-mediated NF-κB activation have been largely unknown. Here, we identify Lys64/66 of OTULIN for linear ubiquitination facilitated in a LUBAC-dependent manner as a necessary event required for OTULIN–LUBAC interaction under unstressed conditions, which becomes deubiquitinated by OTULIN itself in response to genotoxic stress. Furthermore, this self-deubiquitination of OTULIN occurs intermolecularly, mediated by OTULIN dimerization, resulting in the subsequent dissociation of OTULIN from the LUBAC complex and NF-κB overactivation. Oxidative stress induces OTULIN dimerization via cysteine-mediated covalent disulfide bonds. Our study reveals that the status of the physical interaction between OTULIN and LUBAC is a crucial determining factor for the genotoxic NF-κB signaling, as measured by cell survival and proliferation, while OTULIN loss of function resulting from its dimerization and deubiquitination leads to a dissociation of OTULIN from the LUBAC complex. Of note, similar molecular mechanisms apply to the inflammatory NF-κB signaling in response to tumor necrosis factor α. Hence, a fuller understanding of the detailed molecular mechanisms underlying the disruption of the OTULIN–LUBAC interaction will be instrumental for developing future therapeutic strategies against cancer chemoresistance and necroptotic processes pertinent to numerous human diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6134ef09fad1f8f430d8715eadd88fabTest
https://doi.org/10.1073/pnas.2123097119Test

المؤلفون: Infante, Paola, Faedda, Roberta, Bernardi, Flavia, Bufalieri, Francesca, Lospinoso Severini, Ludovica, Alfonsi, Romina, Mazzà, Daniela, Siler, Mariangela, Coni, Sonia, Po, Agnese, Petroni, Marialaura, Ferretti, Elisabetta, Mori, Mattia, De Smaele, Enrico, Canettieri, Gianluca, Capalbo, Carlo, Maroder, Marella, Screpanti, Isabella, Kool, Marcel, Pfister, Stefan M, Guardavaccaro, Daniele, Gulino, Alberto, Di Marcotullio, Lucia

المساهمون: Infante, Paola, Faedda, Roberta, Bernardi, Flavia, Bufalieri, Francesca, Lospinoso Severini, Ludovica, Alfonsi, Romina, Mazzà, Daniela, Siler, Mariangela, Coni, Sonia, Po, Agnese, Petroni, Marialaura, Ferretti, Elisabetta, Mori, Mattia, De Smaele, Enrico, Canettieri, Gianluca, Capalbo, Carlo, Maroder, Marella, Screpanti, Isabella, Kool, Marcel, Pfister, Stefan M, Guardavaccaro, Daniele, Gulino, Alberto, Di Marcotullio, Lucia

مصطلحات موضوعية: Amino Acid Motif, Animal, Carcinogenesi, Female, Hedgehog Protein, Human, Medulloblastoma, Mice, Inbred BALB C, Inbred NOD, Knockout, SCID, Repressor Protein, Signal Transduction, Ubiquitin-Protein Ligase, Ubiquitination, beta-Arrestin 2

الوصف: Suppressor of Fused (SuFu), a tumour suppressor mutated in medulloblastoma, is a central player of Hh signalling, a pathway crucial for development and deregulated in cancer. Although the control of Gli transcription factors by SuFu is critical in Hh signalling, our understanding of the mechanism regulating this key event remains limited. Here, we show that the Itch/β-arrestin2 complex binds SuFu and induces its Lys63-linked polyubiquitylation without affecting its stability. This process increases the association of SuFu with Gli3, promoting the conversion of Gli3 into a repressor, which keeps Hh signalling off. Activation of Hh signalling antagonises the Itch-dependent polyubiquitylation of SuFu. Notably, different SuFu mutations occurring in medulloblastoma patients are insensitive to Itch activity, thus leading to deregulated Hh signalling and enhancing medulloblastoma cell growth. Our findings uncover mechanisms controlling the tumour suppressive functions of SuFu and reveal that their alterations are implicated in medulloblastoma tumorigenesis.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/29515120; info:eu-repo/semantics/altIdentifier/wos/WOS:000426899000002; volume:9; issue:1; firstpage:976; lastpage:992; numberofpages:17; journal:NATURE COMMUNICATIONS; http://hdl.handle.net/11562/992664Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85044632076

الإتاحة: https://doi.org/10.1038/s41467-018-03339-0Test
http://hdl.handle.net/11562/992664Test

المؤلفون: Xi Li, Wenhua Xie, Mengyao Ma

المصدر: International Journal of General Medicine, Vol Volume 14, Pp 3163-3176 (2021)
International Journal of General Medicine

مصطلحات موضوعية: autophagy, Medicine (General), business.industry, Fatty liver, Autophagy, International Journal of General Medicine, General Medicine, Computational biology, nafld, medicine.disease, R5-920, medicine, geo data, Steatohepatitis, KEGG, Signal transduction, hub gene, business, Ubiquitin protein ligase binding, Gene, Late endosome, Original Research

الوصف: Mengyao Ma, Wenhua Xie, Xi Li Department of Laboratory Medicine, Biology Science Institutes, Chongqing Medical University, Chongqing, 400032, People’s Republic of ChinaCorrespondence: Xi LiInstitute of Life Sciences, Chongqing Medical University, Chongqing, 400032, People’s Republic of ChinaTel +8613764350606Email lixi@shmu.edu.cnBackground: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Autophagy plays a vital role in NAFLD development and progression. We aimed to establish a novel autophagy-related gene (ARG) signature as a therapeutic target in NAFLD patients based on high-throughput sequencing data.Methods: ARGs obtained from the HAMdb and high-sequencing data obtained from the Gene Expression Omnibus (GEO) database were analyzed to identify differentially expressed ARGs (DEARGs) between normal and NASH tissues. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to explore potential biological and pathological functions of DEARGs. The protein–protein interaction (PPI) network of the DEARGs was established through the STRING website, and visualized by Cytoscape. In addition, hub genes were validated by an independent dataset GSE89632. Finally, we performed Gene Set Variation Analysis (GSVA) pathway-related analysis to identify the pivotal signaling pathways and genes for the progression of non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH).Results: A total of 76 DEARGs were identified in the GSE126848 dataset, of which 45 genes were upregulated and 31 genes were downregulated. GO analysis showed that the biological functions of DEARGs focused primarily on autophagy, cellular response to external stimulus, fibroblast proliferation, late endosome, and ubiquitin protein ligase binding. KEGG pathway analysis showed that these DEARGs were mainly involved in the apoptosis, PI3K-Akt signaling pathway, and estrogen signaling pathway. Among DEGs, 9 most closely related genes were identified from the PPI network. Furthermore, NOS3, IGF1, VAMP8, FOS, and HMOX1 were verified in the GSE89632 dataset. At last, the MAPK signal pathway was identified as important pathway, and JUN was identified as a key gene involved in the progression from NAFL to NASH.Conclusion: This study may provide credible molecular biomarkers in terms of screening and diagnosis for NAFLD. Meanwhile, it also serves as a basis for exploring the molecular mechanisms underlying the progression of NAFL to NASH.Keywords: GEO data, autophagy, NAFLD, hub gene

وصف الملف: text/html

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7040e7fe348c75de996d4564ed60a659Test
https://www.dovepress.com/identification-of-autophagy-related-genes-in-the-progression-from-non--peer-reviewed-fulltext-article-IJGMTest