{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMARCHF7 (also known as axotrophin) is a RING-CH‐type E3 ubiquitin ligase that plays a pivotal role in cellular protein homeostasis. It undergoes autoubiquitylation and is subject to regulation in a compartment‐specific manner via the action of deubiquitylating enzymes such as USP9X in the cytosol and USP7 in the nucleus, ensuring its stabilization and proper function. In addition, MARCHF7 is implicated in modulating membrane trafficking and receptor turnover, as exemplified by its requirement for the targeted degradation of the leukemia inhibitory factor (LIF) receptor, a key event influencing T cell responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer-related contexts, MARCHF7 emerges as a multifunctional oncoprotein. It stabilizes Mdm2 by catalyzing Lys63-linked polyubiquitination, thereby enhancing Mdm2-dependent degradation of the tumor suppressor p53 and affecting cell proliferation, DNA damage-induced apoptosis, and tumorigenesis. Overexpression of MARCHF7 has also been linked to increased invasion and metastasis in various epithelial cancers including ovarian, endometrial, and esophageal squamous cell carcinoma by modulating key regulators of epithelial-mesenchymal transition such as E-cadherin and Snail, and its high levels correlate with poorer prognoses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cellular growth and transformation, MARCHF7 is notable for influencing immune regulation. Evidence from transplantation tolerance models demonstrates that MARCHF7 affects T cell function by modulating Foxp3 expression, suggesting that its expression is associated with regulatory T cell development and may inversely correlate with graft-versus-host disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMARCHF7 has also been identified as a host factor interacting with viral proteins. Notably, it was found to bind the foot-and-mouth disease virus 2C protein in a yeast two-hybrid screen, a finding that broadens our understanding of how viral proteins may exploit host ubiquitin systems for replication."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent studies further implicate MARCHF7 in the regulation of autophagy. It promotes mixed polyubiquitination of ATG14 at multiple sites—primarily via K6, K11, and K63 linkages—leading to insoluble aggregation of ATG14 and a consequent reduction in its interaction with STX17, thus diminishing autophagy flux. Loss of MARCHF7 function results in a marked decrease in aggresome-like induced structures, highlighting its potential impact on the autophagic clearance of protein aggregates, an area of significant relevance to neurodegenerative diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "James A Nathan, Soma Sengupta, Stephen A Wood, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ubiquitin E3 ligase MARCH7 is differentially regulated by the deubiquitylating enzymes USP7 and USP9X."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0854.2008.00747.x"}], "href": "https://doi.org/10.1111/j.1600-0854.2008.00747.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18410486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18410486"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Cristina A Szigyarto, Paul Sibbons, Gill Williams, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The E3 ligase axotrophin/MARCH-7: protein expression profiling of human tissues reveals links to adult stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Histochem Cytochem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1369/jhc.2009.954420"}], "href": "https://doi.org/10.1369/jhc.2009.954420"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19901269"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19901269"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Li Zhang, Hua Wang, Lin Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of USP7 and MARCH7 Is Correlated with Poor Prognosis in Epithelial Ovarian Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tohoku J Exp Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1620/tjem.239.165"}], "href": "https://doi.org/10.1620/tjem.239.165"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27302477"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27302477"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kailiang Zhao, Yang Yang, Guang Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the Mdm2-p53 pathway by the ubiquitin E3 ligase MARCH7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201744465"}], "href": "https://doi.org/10.15252/embr.201744465"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29295817"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29295817"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ling Liu, Jianguo Hu, Tinghe Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-27b-3p/MARCH7 regulates invasion and metastasis of endometrial cancer cells through Snail-mediated pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Biochim Biophys Sin (Shanghai) (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/abbs/gmz030"}], "href": "https://doi.org/10.1093/abbs/gmz030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31006800"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31006800"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shivam Singh, Arjumand Bano, Anoop Saraya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of MARCH7 with tumor progression and T-cell infiltration in esophageal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Oncol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12032-022-01938-y"}], "href": "https://doi.org/10.1007/s12032-022-01938-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36583798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36583798"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Poorni A D S Muthukumarana, Gary E Lyons, Yuji Miura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence for functional inter-relationships between FOXP3, leukaemia inhibitory factor, and axotrophin/MARCH-7 in transplantation tolerance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Immunopharmacol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.intimp.2006.09.015"}], "href": "https://doi.org/10.1016/j.intimp.2006.09.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17161353"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17161353"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sonalika Mahajan, Gaurav Kumar Sharma, Kavita Bora, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of novel interactions between host and non-structural protein 2C of foot-and-mouth disease virus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gen Virol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1099/jgv.0.001577"}], "href": "https://doi.org/10.1099/jgv.0.001577"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33729124"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33729124"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xue Shi, Xiaofei Zhang "}, {"type": "b", "children": [{"type": "t", "text": "Control of ATG14 solubility and autophagy by MARCHF7/MARCH7-mediated ubiquitination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2023.2278414"}], "href": "https://doi.org/10.1080/15548627.2023.2278414"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37915253"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37915253"}]}]}]}