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However, surprisingly little is known about the effects of host regulators on ACE2 localization, expression, and the associated influence on SARS-CoV-2 infection. Here we identify that ACE2 expression levels are regulated by the E3 ligase MDM2 and that MDM2 levels indirectly influence infection with SARS-CoV-2. Genetic depletion of MDM2 elevated ACE2 expression levels, which strongly promoted infection with all SARS-CoV-2 isolates tested. SARS-CoV-2 spike-pseudotyped viruses and the uptake of non-replication-competent virus-like particles showed that MDM2 affects the viral uptake process. MDM2 ubiquitinates Lysine 788 of ACE2 to induce proteasomal degradation, and degradation of this residue led to higher ACE2 expression levels and superior virus particle uptake. Our study illustrates that cellular regulators of ACE2 stability, such as MDM2, play an important role in defining the infection capabilities of SARS-CoV-2.<\/jats:p>","DOI":"10.3390\/v15081763","type":"journal-article","created":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T10:14:38Z","timestamp":1692353678000},"page":"1763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["MDM2 Influences ACE2 Stability and SARS-CoV-2 Uptake"],"prefix":"10.3390","volume":"15","author":[{"given":"Quirin","family":"Emslander","sequence":"first","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1280-4722","authenticated-orcid":false,"given":"Karsten","family":"Krey","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabri","family":"Hamad","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Maidl","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lila","family":"Oubraham","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Hesse","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Henrici","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Austen","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Mergner","sequence":"additional","affiliation":[{"name":"BayBioMS@MRI\u2014Bavarian Center for Biomolecular Mass Spectrometry at Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7710-4789","authenticated-orcid":false,"given":"Vincent","family":"Grass","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0166-1367","authenticated-orcid":false,"given":"Andreas","family":"Pichlmair","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany"},{"name":"German Centre for Infection Research (DZIF), Partner site Munich, 81675 Munich, Germany"},{"name":"Center of Immunology of Viral Infection (CiViA), Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"D\u2019Ardes, D., Boccatonda, A., Rossi, I., Guagnano, M.T., Santilli, F., Cipollone, F., and Bucci, M. (2020). COVID-19 and RAS: Unravelling an Unclear Relationship. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21083003"},{"key":"ref_2","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/s41392-021-00740-y","article-title":"ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker","volume":"6","author":"Chen","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"publisher","first-page":"e107821","DOI":"10.15252\/embj.2021107821","article-title":"TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells","volume":"40","author":"Koch","year":"2021","journal-title":"EMBO J."},{"key":"ref_5","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1038\/s41467-020-15562-9","article-title":"Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV","volume":"11","author":"Ou","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 entry into cells","volume":"23","author":"Jackson","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"publisher","first-page":"e28116","DOI":"10.1002\/jmv.28116","article-title":"Key mutations on spike protein altering ACE2 receptor utilization and potentially expanding host range of emerging SARS-CoV-2 variants","volume":"95","author":"Wang","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_8","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1126\/science.abe8499","article-title":"SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo","volume":"370","author":"Hou","year":"2020","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.cell.2020.06.043","article-title":"Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus","volume":"182","author":"Korber","year":"2020","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s40249-020-00662-x","article-title":"Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues","volume":"9","author":"Li","year":"2020","journal-title":"Infect. Dis. Poverty"},{"key":"ref_11","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1038\/s41422-020-00460-y","article-title":"AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells","volume":"31","author":"Wang","year":"2021","journal-title":"Cell Res."},{"key":"ref_12","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1126\/science.abd2985","article-title":"Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity","volume":"370","author":"Ojha","year":"2020","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"publisher","first-page":"e0230822","DOI":"10.1128\/mbio.02308-22","article-title":"Neuropilin-1 Mediates SARS-CoV-2 Infection of Astrocytes in Brain Organoids, Inducing Inflammation Leading to Dysfunction and Death of Neurons","volume":"13","author":"Kong","year":"2022","journal-title":"mBio"},{"key":"ref_14","doi-asserted-by":"publisher","first-page":"e54305","DOI":"10.15252\/embr.202154305","article-title":"ADAM10 and ADAM17 promote SARS-CoV-2 cell entry and spike protein-mediated lung cell fusion","volume":"23","author":"Jocher","year":"2022","journal-title":"EMBO Rep."},{"key":"ref_15","doi-asserted-by":"publisher","first-page":"254","DOI":"10.7555\/JBR.27.20130030","article-title":"The MDM2-p53 pathway revisited","volume":"27","author":"Nag","year":"2013","journal-title":"J. Biomed. Res."},{"key":"ref_16","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1038\/s41586-021-03493-4","article-title":"Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV","volume":"594","author":"Stukalov","year":"2021","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/nmeth.3047","article-title":"Improved vectors and genome-wide libraries for CRISPR screening","volume":"11","author":"Sanjana","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_18","doi-asserted-by":"publisher","first-page":"e111608","DOI":"10.15252\/embj.2022111608","article-title":"Attenuation of SARS-CoV-2 replication and associated inflammation by concomitant targeting of viral and host cap 2\u2019-O-ribose methyltransferases","volume":"41","author":"Bergant","year":"2022","journal-title":"EMBO J."},{"key":"ref_19","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1038\/ni.2048","article-title":"IFIT1 is an antiviral protein that recognizes 5\u2019-triphosphate RNA","volume":"12","author":"Pichlmair","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_20","doi-asserted-by":"publisher","first-page":"3464","DOI":"10.1128\/JVI.02914-13","article-title":"Virulence factor NSs of rift valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH","volume":"88","author":"Kainulainen","year":"2014","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"publisher","first-page":"pgac045","DOI":"10.1093\/pnasnexus\/pgac045","article-title":"Quantitation of SARS-CoV-2 neutralizing antibodies with a virus-free, authentic test","volume":"1","author":"Roessler","year":"2022","journal-title":"PNAS Nexus"},{"key":"ref_22","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.3201\/eid2608.201246","article-title":"US CDC Real-Time Reverse Transcription PCR Panel for Detection of Severe Acute Respiratory Syndrome Coronavirus 2","volume":"26","author":"Lu","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"publisher","first-page":"2453","DOI":"10.1210\/en.2006-1287","article-title":"Synergistic expression of angiotensin-converting enzyme (ACE) and ACE2 in human renal tissue and confounding effects of hypertension on the ACE to ACE2 ratio","volume":"148","author":"Wakahara","year":"2007","journal-title":"Endocrinology"},{"key":"ref_24","doi-asserted-by":"publisher","first-page":"3271","DOI":"10.3892\/mmr.2018.9329","article-title":"MNX1 reduces sensitivity to anoikis by activating TrkB in human glioma cells","volume":"18","author":"Jiang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_25","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1128\/JVI.01691-06","article-title":"The ORF7b protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is expressed in virus-infected cells and incorporated into SARS-CoV particles","volume":"81","author":"Schaecher","year":"2007","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"publisher","first-page":"654709","DOI":"10.3389\/fmicb.2021.654709","article-title":"SARS-CoV-2 Accessory Protein ORF7b Mediates Tumor Necrosis Factor-\u03b1-Induced Apoptosis in Cells","volume":"12","author":"Yang","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_27","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/s41421-021-00268-z","article-title":"The SARS-CoV-2 protein ORF3a inhibits fusion of autophagosomes with lysosomes","volume":"7","author":"Zhang","year":"2021","journal-title":"Cell Discov."},{"key":"ref_28","doi-asserted-by":"publisher","first-page":"854567","DOI":"10.3389\/fmicb.2022.854567","article-title":"Understanding the Role of SARS-CoV-2 ORF3a in Viral Pathogenesis and COVID-19","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref_29","unstructured":"Teng, F.Y.H., Wang, Y., and Tang, B.L. (2021). The syntaxins. Genome Biol., 2."},{"key":"ref_30","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1083\/jcb.200110081","article-title":"Early\/recycling endosomes-to-TGN transport involves two SNARE complexes and a Rab6 isoform","volume":"156","author":"Mallard","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_31","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1002\/j.1460-2075.1991.tb08049.x","article-title":"A role of the latent TGF-beta 1-binding protein in the assembly and secretion of TGF-beta 1","volume":"10","author":"Miyazono","year":"1991","journal-title":"EMBO J."},{"key":"ref_32","doi-asserted-by":"publisher","first-page":"902713","DOI":"10.3389\/fmed.2022.902713","article-title":"Therapeutic potential of the MDM2 inhibitor Nutlin-3 in counteracting SARS-CoV-2 infection of the eye through p53 activation","volume":"9","author":"Zauli","year":"2022","journal-title":"Front. Med."},{"key":"ref_33","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.3389\/fphar.2020.01156","article-title":"Rationale for Considering Oral Idasanutlin as a Therapeutic Option for COVID-19 Patients","volume":"11","author":"Zauli","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhao, X., Zheng, S., Chen, D., Zheng, M., Li, X., Li, G., Lin, H., Chang, J., Zeng, H., and Guo, J.-T. (2020). LY6E Restricts Entry of Human Coronaviruses, Including Currently Pandemic SARS-CoV-2. J. Virol., 94.","DOI":"10.1128\/JVI.00562-20"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Goto, K., Nishitsuji, H., Sugiyama, M., Nishida, N., Mizokami, M., and Shimotohno, K. (2020). Orchestration of Intracellular Circuits by G Protein-Coupled Receptor 39 for Hepatitis B Virus Proliferation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165661"},{"key":"ref_36","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.exger.2017.09.006","article-title":"Changes in Zn homeostasis during long term culture of primary endothelial cells and effects of Zn on endothelial cell senescence","volume":"99","author":"Malavolta","year":"2017","journal-title":"Exp. Gerontol."},{"key":"ref_37","doi-asserted-by":"publisher","first-page":"10471","DOI":"10.1038\/s41598-019-46952-9","article-title":"The transporters SLC35A1 and SLC30A1 play opposite roles in cell survival upon VSV virus infection","volume":"9","author":"Moskovskich","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hornbeck, P.V., Zhang, B., Murray, B., Kornhauser, J.M., Latham, V., and Skrzypek, E. (2015). PhosphoSitePlus, 2014: Mutations, PTMs and recalibrations. Nucleic Acids Res., 43.","DOI":"10.1093\/nar\/gku1267"},{"key":"ref_39","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1161\/CIRCULATIONAHA.120.048191","article-title":"MDM2-Mediated Ubiquitination of Angiotensin-Converting Enzyme 2 Contributes to the Development of Pulmonary Arterial Hypertension","volume":"142","author":"Shen","year":"2020","journal-title":"Circulation"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Longhitano, L., Tibullo, D., Giallongo, C., Lazzarino, G., Tartaglia, N., Galimberti, S., Li Volti, G., Palumbo, G.A., and Liso, A. (2020). Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103622"},{"key":"ref_41","doi-asserted-by":"publisher","first-page":"e101994","DOI":"10.15252\/embj.2019101994","article-title":"Mammalian Atg8 proteins regulate lysosome and autolysosome biogenesis through SNAREs","volume":"38","author":"Gu","year":"2019","journal-title":"EMBO J."},{"key":"ref_42","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1002\/jcp.22286","article-title":"Syntaxin 16: Unraveling cellular physiology through a ubiquitous SNARE molecule","volume":"225","author":"Chen","year":"2010","journal-title":"J. Cell. Physiol."},{"key":"ref_43","doi-asserted-by":"publisher","first-page":"298","DOI":"10.3390\/v2010298","article-title":"Dual Role of p53 in Innate Antiviral Immunity","volume":"2","author":"Rivas","year":"2010","journal-title":"Viruses"},{"key":"ref_44","doi-asserted-by":"publisher","first-page":"6428","DOI":"10.4049\/jimmunol.1101459","article-title":"p53 serves as a host antiviral factor that enhances innate and adaptive immune responses to influenza A virus","volume":"187","author":"Pazos","year":"2011","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1007\/s11684-021-0837-6","article-title":"Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells","volume":"15","author":"Wang","year":"2021","journal-title":"Front. Med."},{"key":"ref_46","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.hjc.2020.05.007","article-title":"Outbreak of SARS-CoV2: Pathogenesis of infection and cardiovascular involvement","volume":"62","author":"Amirfakhryan","year":"2021","journal-title":"Hellenic J. Cardiol."},{"key":"ref_47","doi-asserted-by":"publisher","first-page":"e87877","DOI":"10.1172\/jci.insight.87877","article-title":"Systems biology analysis reveals role of MDM2 in diabetic nephropathy","volume":"1","author":"Saito","year":"2016","journal-title":"JCI Insight"},{"key":"ref_48","doi-asserted-by":"publisher","first-page":"838213","DOI":"10.3389\/fcimb.2022.838213","article-title":"Mechanisms of SARS-CoV-2 Infection-Induced Kidney Injury: A Literature Review","volume":"12","author":"He","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_49","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s41586-020-2521-4","article-title":"Factors associated with COVID-19-related death using OpenSAFELY","volume":"584","author":"Williamson","year":"2020","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"publisher","first-page":"2858","DOI":"10.1038\/s41375-020-0949-z","article-title":"MDM2 inhibition: An important step forward in cancer therapy","volume":"34","author":"Konopleva","year":"2020","journal-title":"Leukemia"},{"key":"ref_51","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/s41392-021-00639-8","article-title":"Identification of proteasome and caspase inhibitors targeting SARS-CoV-2 M","volume":"6","author":"Wang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_52","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/s41392-022-01156-y","article-title":"Multiomics approach reveals the ubiquitination-specific processes hijacked by SARS-CoV-2","volume":"7","author":"Xu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Gro\u00dfe, M., Setz, C., Rauch, P., Auth, J., Morokutti-Kurz, M., Temchura, V., and Schubert, U. (2022). Inhibitors of Deubiquitinating Enzymes Interfere with the SARS-CoV-2 Papain-like Protease and Block Virus Replication In Vitro. 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