{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:20:34Z","timestamp":1782300034791,"version":"3.54.5"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Osteoarthritis (OA) is the most widespread joint disorder worldwide. It is a major cause of lower limb mobility issues in the elderly. With the ongoing aging of the global population and the increasing prevalence of obesity, the disease burden associated with OA is expected to rise significantly. E3 ubiquitin ligases (E3s) play a crucial role in protein ubiquitination. They identify specific substrates and attach ubiquitin molecules to substrates, thus modulating protein stability, function, and cellular localization. E3s can be classified into three main types: RING-, HECT-, and RBR-type E3s. Growing evidence indicates that E3s affect OA by regulating the degradation of extracellular matrix (ECM) proteins and inflammatory responses. This review highlights the functions and underlying mechanisms of E3s in OA, aiming to provide new therapeutic insights for the treatment of OA.<\/jats:p>","DOI":"10.3389\/fcell.2025.1665313","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T05:28:20Z","timestamp":1755840500000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["The multifaceted roles of E3 ubiquitin ligases in osteoarthritis"],"prefix":"10.3389","volume":"13","author":[{"given":"Zheng","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.molcel.2024.12.015","article-title":"Ubiquitin-A structural perspective","volume":"85","author":"Agrata","year":"2025","journal-title":"Mol. Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.3390\/cells13131161","article-title":"Tumor necrosis factor-alpha modulates expression of genes involved in cytokines and chemokine pathways in proliferative myoblast cells","volume":"13","author":"Alvarez","year":"2024","journal-title":"Cells"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.berh.2005.09.007","article-title":"Osteoarthritis: epidemiology","volume":"20","author":"Arden","year":"2006","journal-title":"Best. Pract. Res. Clin. Rheumatol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1074\/jbc.M116.756601","article-title":"Cytokine-induced MMP13 expression in human chondrocytes is dependent on activating transcription factor 3 (ATF3) regulation","volume":"292","author":"Chan","year":"2017","journal-title":"J. Biol. Chem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"174876","DOI":"10.1016\/j.ejphar.2022.174876","article-title":"Cbl-b modulated TrkA ubiquitination and function in the dorsal root ganglion of mice","volume":"921","author":"Chen","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1186\/s13046-023-02767-1","article-title":"FBXW7 in breast cancer: mechanism of action and therapeutic potential","volume":"42","author":"Chen","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"734","DOI":"10.3390\/cells8070734","article-title":"NF-\u03baB signaling pathways in osteoarthritic cartilage destruction","volume":"8","author":"Choi","year":"2019","journal-title":"Cells"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1002\/humu.22117","article-title":"Locus-specific mutation databases for neurodegenerative brain diseases","volume":"33","author":"Cruts","year":"2012","journal-title":"Hum. Mutat."},{"key":"B9","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1161\/CIRCRESAHA.115.306993","article-title":"Hrd1 and ER-associated protein degradation, ERAD, are critical elements of the adaptive ER stress response in cardiac myocytes","volume":"117","author":"Doroudgar","year":"2015","journal-title":"Circ. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"36300","DOI":"10.1074\/jbc.M803196200","article-title":"Regulation of cartilage-specific gene expression in human chondrocytes by SirT1 and nicotinamide phosphoribosyltransferase","volume":"283","author":"Dvir-Ginzberg","year":"2008","journal-title":"J. Biol. Chem."},{"key":"B11","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/s41419-018-0432-1","article-title":"circHECTD1 promotes the silica-induced pulmonary endothelial-mesenchymal transition via HECTD1","volume":"9","author":"Fang","year":"2018","journal-title":"Cell Death Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e13600","DOI":"10.1111\/cpr.13600","article-title":"Signalling interaction between \u03b2-catenin and other signalling molecules during osteoarthritis development","volume":"57","author":"Feng","year":"2024","journal-title":"Cell Prolif."},{"key":"B13","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/s41531-024-00707-0","article-title":"PARKIN is not required to sustain OXPHOS function in adult mammalian tissues","volume":"10","author":"Filograna","year":"2024","journal-title":"npj Parkinson's Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1152\/physrev.00012.2016","article-title":"Ubiquitination and the regulation of membrane proteins","volume":"97","author":"Foot","year":"2017","journal-title":"Physiol. Rev."},{"key":"B15","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.semcancer.2019.12.023","article-title":"The functions and regulation of Smurfs in cancers","volume":"67","author":"Fu","year":"2020","journal-title":"Seminars Cancer Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1080\/13543776.2024.2412567","article-title":"CBL-B - an upcoming immune-oncology target","volume":"35","author":"Fusco","year":"2025","journal-title":"Expert Opin. Ther. Pat."},{"key":"B17","doi-asserted-by":"publisher","first-page":"13648","DOI":"10.3390\/ijms232113648","article-title":"E3 ubiquitin ligase FBXO3 drives neuroinflammation to aggravate cerebral ischemia\/reperfusion injury","volume":"23","author":"Gao","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e508","DOI":"10.1016\/S2665-9913(23)00163-7","article-title":"Global, regional, and national burden of osteoarthritis, 1990-2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021","volume":"5","year":"2023","journal-title":"Lancet Rheumatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3390\/biology9080194","article-title":"Pathogenesis of osteoarthritis: risk factors, regulatory pathways in chondrocytes, and experimental models","volume":"9","author":"He","year":"2020","journal-title":"Biol. (Basel)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1451737","DOI":"10.3389\/fpubh.2024.1451737","article-title":"The association between accelerated biological aging and the risk of osteoarthritis: a cross-sectional study","volume":"12","author":"He","year":"2024","journal-title":"Front. Public Health"},{"key":"B21","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41419-023-06417-4","article-title":"The E3 ubiquitin ligase Itch regulates death receptor and cholesterol trafficking to affect TRAIL-mediated apoptosis","volume":"15","author":"Holloway","year":"2024","journal-title":"Cell Death Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1146\/annurev-biochem-051810-094654","article-title":"Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions","volume":"81","author":"Husnjak","year":"2012","journal-title":"Annu. Rev. Biochem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.matbio.2015.03.004","article-title":"Membrane-type matrix metalloproteinases: their functions and regulations","author":"Itoh","year":"2015","journal-title":"Matrix Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1080\/08830185.2022.2102618","article-title":"The role of TRIM59 in immunity and immune-related diseases","volume":"43","author":"Jin","year":"2024","journal-title":"Int. Rev. Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1016\/s1097-2765(00)00134-9","article-title":"Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation","volume":"6","author":"Kavsak","year":"2000","journal-title":"Mol. Cell"},{"key":"B26","doi-asserted-by":"publisher","first-page":"a008888","DOI":"10.1101\/cshperspect.a008888","article-title":"Genetics of Parkinson's disease","volume":"2","author":"Klein","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/s0014-5793(02)03654-2","article-title":"Cellular activation of proMMP-13 by MT1-MMP depends on the C-terminal domain of MMP-13","volume":"532","author":"Kn\u00e4uper","year":"2002","journal-title":"FEBS Lett."},{"key":"B28","doi-asserted-by":"publisher","first-page":"521754","DOI":"10.1155\/2014\/521754","article-title":"Transforming growth factor-beta and matrix metalloproteinases: functional interactions in tumor stroma-infiltrating myeloid cells","volume":"2014","author":"Krstic","year":"2014","journal-title":"ScientificWorldJournal"},{"key":"B29","doi-asserted-by":"publisher","first-page":"119827","DOI":"10.1016\/j.bbamcr.2024.119827","article-title":"E3 ubiquitin ligases and deubiquitinases in colorectal cancer: emerging molecular insights and therapeutic opportunities","volume":"1871","author":"Kumar","year":"2024","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1002\/art.42369","article-title":"HECTD1-Mediated ubiquitination and degradation of Rubicon regulates autophagy and osteoarthritis pathogenesis","volume":"75","author":"Liao","year":"2023","journal-title":"Arthritis Rheumatol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1016\/j.joca.2021.04.009","article-title":"The E3 ubiquitin ligase Itch limits the progression of post-traumatic osteoarthritis in mice by inhibiting macrophage polarization","volume":"29","author":"Lin","year":"","journal-title":"Osteoarthr. Cartil."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e13306","DOI":"10.1111\/acel.13306","article-title":"JUNB-FBXO21-ERK axis promotes cartilage degeneration in osteoarthritis by inhibiting autophagy","volume":"20","author":"Lin","year":"","journal-title":"Aging Cell"},{"key":"B33","doi-asserted-by":"publisher","first-page":"963689720943604","DOI":"10.1177\/0963689720943604","article-title":"Knockdown of TRIM8 attenuates IL-1\u03b2-induced inflammatory response in osteoarthritis chondrocytes through the inactivation of NF-\u03baB pathway","volume":"29","author":"Liu","year":"2020","journal-title":"Cell Transpl."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2801","DOI":"10.1016\/j.csbj.2023.04.022","article-title":"TRIM56 coiled-coil domain structure provides insights into its E3 ligase functions","volume":"21","author":"Lou","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"B35","doi-asserted-by":"publisher","first-page":"111191","DOI":"10.1016\/j.intimp.2023.111191","article-title":"RNF125, transcriptionally regulated by NFATC2, alleviates osteoarthritis via inhibiting the Wnt\/\u03b2-catenin signaling pathway through degrading TRIM14","volume":"125","author":"Lv","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"110597","DOI":"10.1016\/j.isci.2024.110597","article-title":"Targeting Parkin-regulated metabolomic change in cartilage in the treatment of osteoarthritis","volume":"27","author":"Ma","year":"2024","journal-title":"iScience"},{"key":"B37","doi-asserted-by":"publisher","first-page":"284873","DOI":"10.1155\/2013\/284873","article-title":"The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis","volume":"2013","author":"Maldonado","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"B38","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1097\/ALN.0b013e31821b1ac5","article-title":"Antagonism of nerve growth factor-TrkA signaling and the relief of pain","volume":"115","author":"Mantyh","year":"2011","journal-title":"Anesthesiology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1002\/pro.3532","article-title":"Unique RING finger structure from the human HRD1 protein","volume":"28","author":"Miyamoto","year":"2019","journal-title":"Protein Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2429","DOI":"10.1038\/s41467-019-10177-1","article-title":"Wwp2 maintains cartilage homeostasis through regulation of Adamts5","volume":"10","author":"Mokuda","year":"2019","journal-title":"Nat. Commun."},{"key":"B41","doi-asserted-by":"publisher","first-page":"100090","DOI":"10.1016\/j.bbiosy.2024.100090","article-title":"The role of inflammatory mediators and matrix metalloproteinases (MMPs) in the progression of osteoarthritis","volume":"13","author":"Mukherjee","year":"2024","journal-title":"Biomater. Biosyst."},{"key":"B42","doi-asserted-by":"publisher","first-page":"14820","DOI":"10.3390\/ijms241914820","article-title":"The dual role of the innate immune system in the effectiveness of mRNA therapeutics","volume":"24","author":"Muslimov","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"896099","DOI":"10.3389\/fmolb.2022.896099","article-title":"Insights into the role of matrix metalloproteinases in cancer and its various therapeutic aspects: a review","volume":"9","author":"Mustafa","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"eaaz6893","DOI":"10.1126\/sciadv.aaz6893","article-title":"Impact of mRNA chemistry and manufacturing process on innate immune activation","volume":"6","author":"Nelson","year":"2020","journal-title":"Sci. Adv."},{"key":"B45","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/s41586-018-0026-1","article-title":"Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity","volume":"556","author":"Pao","year":"2018","journal-title":"Nature"},{"key":"B46","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.1042\/BST20230324","article-title":"Human E3 ubiquitin ligases: accelerators and brakes for SARS-CoV-2 infection","volume":"52","author":"Pellman","year":"2024","journal-title":"Biochem. Soc. Trans."},{"key":"B47","doi-asserted-by":"publisher","first-page":"109921","DOI":"10.1016\/j.cbi.2022.109921","article-title":"E3 ubiquitin ligase ITCH improves LPS-induced chondrocyte injury by mediating JAG1 ubiquitination in osteoarthritis","volume":"360","author":"Qi","year":"2022","journal-title":"Chem. Biol. Interact."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1002\/stem.2365","article-title":"Vav1 regulates mesenchymal stem cell differentiation decision between adipocyte and chondrocyte via Sirt1","volume":"34","author":"Qu","year":"2016","journal-title":"Stem Cells"},{"key":"B49","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/s41392-024-02002-z","article-title":"Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications","volume":"9","author":"Shi","year":"2024","journal-title":"Signal Transduct. Target Ther."},{"key":"B50","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1186\/s13104-023-06670-y","article-title":"Centriolin interacts with HectD1 in a cell cycle dependent manner","volume":"16","author":"Salas","year":"2023","journal-title":"BMC Res. Notes"},{"key":"B51","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1038\/s41418-020-00706-7","article-title":"Ubiquitin signalling in neurodegeneration: mechanisms and therapeutic opportunities","volume":"28","author":"Schmidt","year":"2021","journal-title":"Cell Death Differ."},{"key":"B52","doi-asserted-by":"publisher","first-page":"117s","DOI":"10.1177\/1947603520967069","article-title":"SMURF1 and SMURF2 in progenitor cells from articular cartilage and meniscus during late-stage osteoarthritis","volume":"13","author":"Schminke","year":"2021","journal-title":"Cartilage"},{"key":"B53","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1146\/annurev.pharmtox.051208.165340","article-title":"Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology","volume":"49","author":"Schwartz","year":"2009","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.1111\/febs.13249","article-title":"Parkin structure and function","volume":"282","author":"Seirafi","year":"2015","journal-title":"Febs J."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1007\/s11010-020-04047-4","article-title":"lncRNA-CRNDE regulates BMSC chondrogenic differentiation and promotes cartilage repair in osteoarthritis through SIRT1\/SOX9","volume":"476","author":"Shi","year":"2021","journal-title":"Mol. Cell Biochem."},{"key":"B56","doi-asserted-by":"publisher","first-page":"11940","DOI":"10.1021\/acs.nanolett.3c04150","article-title":"Structural dynamics of E6AP E3 ligase HECT domain and involvement of a flexible hinge loop in the ubiquitin chain synthesis mechanism","volume":"23","author":"Takeda","year":"2023","journal-title":"Nano Lett."},{"key":"B57","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.bbrc.2020.05.130","article-title":"TRIM59 attenuates IL-1\u03b2-driven cartilage matrix degradation in osteoarthritis via direct suppression of NF-\u03baB and JAK2\/STAT3 signaling pathway","volume":"529","author":"Teng","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B58","doi-asserted-by":"publisher","first-page":"157","DOI":"10.2174\/1568009616666151112122801","article-title":"RING-HECT-and RBR-type E3 ubiquitin ligases: involvement in human cancer","volume":"16","author":"Uchida","year":"2016","journal-title":"Curr. Cancer Drug Targets"},{"key":"B59","doi-asserted-by":"publisher","first-page":"13160","DOI":"10.1038\/s41598-022-16965-y","article-title":"The E3 ubiquitin ligase HECTD1 contributes to cell proliferation through an effect on mitosis","volume":"12","author":"Vaughan","year":"2022","journal-title":"Sci. Rep."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1136\/annrheumdis-2019-216911","article-title":"TGF\u03b2 attenuates cartilage extracellular matrix degradation via enhancing FBXO6-mediated MMP14 ubiquitination","volume":"79","author":"Wang","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"B61","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.1002\/tox.23627","article-title":"miR-219a-5p inhibits the pyroptosis in knee osteoarthritis by inactivating the NLRP3 signaling via targeting FBXO3","volume":"37","author":"Wang","year":"2022","journal-title":"Environ. Toxicol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1002\/jcp.25957","article-title":"The endoplasmic reticulum-associated protein, OS-9, behaves as a lectin in targeting the immature calcium-sensing receptor","volume":"233","author":"Ward","year":"2018","journal-title":"J. Cell Physiol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"3764","DOI":"10.3390\/cancers12123764","article-title":"Ubiquitination and ubiquitin-like modifications in multiple myeloma: biology and therapy","volume":"12","author":"Wirth","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B64","doi-asserted-by":"publisher","first-page":"255","DOI":"10.3390\/biom11020255","article-title":"Highly specialized ubiquitin-like modifications: shedding light into the UFM1 enigma","volume":"11","author":"Witting","year":"2021","journal-title":"Biomolecules"},{"key":"B65","doi-asserted-by":"publisher","first-page":"106278","DOI":"10.1016\/j.intimp.2020.106278","article-title":"UFL1 attenuates IL-1\u03b2-induced inflammatory response in human osteoarthritis chondrocytes","volume":"81","author":"Yang","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13578-018-0245-z","article-title":"Proteomic characterization of endogenous substrates of mammalian ubiquitin ligase Hrd1","volume":"8","author":"Ye","year":"2018","journal-title":"Cell Biosci."},{"key":"B67","doi-asserted-by":"publisher","first-page":"101257","DOI":"10.1016\/j.mam.2024.101257","article-title":"E3 ubiquitin ligase WWP2 as a promising therapeutic target for diverse human diseases","volume":"96","author":"You","year":"2024","journal-title":"Mol. Asp. Med."},{"key":"B68","doi-asserted-by":"publisher","first-page":"101247","DOI":"10.1016\/j.gendis.2024.101247","article-title":"Development of novel osteoarthritis therapy by targeting AMPK-\u03b2-catenin-Runx2 signaling","volume":"12","author":"Zeng","year":"2025","journal-title":"Genes Dis."},{"key":"B69","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.cger.2010.03.001","article-title":"Epidemiology of osteoarthritis","volume":"26","author":"Zhang","year":"2010","journal-title":"Clin. Geriatr. Med."},{"key":"B70","doi-asserted-by":"publisher","first-page":"2727","DOI":"10.7150\/ijbs.48437","article-title":"E3 Ubiquitin ligase NEDD4 family-regulatory network in cardiovascular disease","volume":"16","author":"Zhang","year":"","journal-title":"Int. J. Biol. Sci."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.3892\/ol.2020.11728","article-title":"Function and regulation of F-box\/WD repeat-containing protein 7","volume":"20","author":"Zhang","year":"","journal-title":"Oncol. Lett."},{"key":"B72","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1136\/annrheumdis-2021-221513","article-title":"Mechanical overloading promotes chondrocyte senescence and osteoarthritis development through downregulating FBXW7","volume":"81","author":"Zhang","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"B73","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1146\/annurev-biochem-060815-014922","article-title":"Ubiquitin ligases: structure, function, and regulation","volume":"86","author":"Zheng","year":"2017","journal-title":"Annu. Rev. Biochem."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1665313\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T05:28:21Z","timestamp":1755840501000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1665313\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,22]]},"references-count":73,"alternative-id":["10.3389\/fcell.2025.1665313"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2025.1665313","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,22]]},"article-number":"1665313"}}