{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:03:54Z","timestamp":1760234634814,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Do 343\/7-1"],"award-info":[{"award-number":["Do 343\/7-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The adenovirus type 5 (HAdV-C5) E1 transcription unit encodes regulatory proteins that are essential for viral replication and transformation. Among these, E1A and E1B-55K act as key multifunctional HAdV-C5 proteins involved in various steps of the viral replication cycle and in virus-induced cell transformation. In this context, HAdV-C5-mediated dysregulations of cellular factors such as the tumor suppressors p53 and pRB have been intensively investigated. However, cellular components of downstream events that could affect infection and viral transformation are widely unknown. We recently observed that cellular FAM111B is highly regulated in an E1A-dependent fashion. Intriguingly, previous reports suggest that FAM111B might play roles in tumorigenesis, but its exact functions are not known to date. Here, we set out to investigate the role of FAM111B in HAdV-C5 infections. We found that (i) FAM111B levels are upregulated early and downregulated late during infection, that (ii) FAM111B expression is differentially regulated, that (iii) FAM111B expression levels depend on the presence of E1B-55K and E4orf6 and that (iv) a FAM111B knockdown increases HAdV-C5 replication. Our data indicate that FAM111B acts as an anti-adenoviral host factor that is involved in host cell defense mechanisms in productive HAdV-C5 infection. Moreover, these findings suggest that FAM111B might play an important role in the host antiviral immune response that is counteracted by HAdV-C5 E1B-55K and E4orf6 oncoproteins.<\/jats:p>","DOI":"10.3390\/v13061015","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T03:45:29Z","timestamp":1622432729000},"page":"1015","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Differential Regulation of Cellular FAM111B by Human Adenovirus C Type 5 E1 Oncogenes"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5367-1401","authenticated-orcid":false,"given":"Wing-Hang","family":"Ip","sequence":"first","affiliation":[{"name":"Department of Viral Transformation, Leibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Britta","family":"Wilkens","sequence":"additional","affiliation":[{"name":"Department of Viral Transformation, Leibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia","family":"Solomatina","sequence":"additional","affiliation":[{"name":"Department of Viral Transformation, Leibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Viral Transformation, Leibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Melling","sequence":"additional","affiliation":[{"name":"Department of Viral Transformation, Leibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5867-0128","authenticated-orcid":false,"given":"Paloma","family":"Hidalgo","sequence":"additional","affiliation":[{"name":"Department of Viral Transformation, Leibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0698-5395","authenticated-orcid":false,"given":"Luca D.","family":"Bertzbach","sequence":"additional","affiliation":[{"name":"Department of Viral Transformation, Leibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Speiseder","sequence":"additional","affiliation":[{"name":"Department of Viral Transformation, Leibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Dobner","sequence":"additional","affiliation":[{"name":"Department of Viral Transformation, Leibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1128\/CMR.00116-13","article-title":"Adenovirus infections in immunocompetent and immunocompromised patients","volume":"27","author":"Lion","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.virol.2017.01.013","article-title":"Normal human cell proteins that interact with the adenovirus type 5 E1B 55kDa protein","volume":"504","author":"Hung","year":"2017","journal-title":"Virology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.ajhg.2013.10.013","article-title":"Mutations in FAM111B cause hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis","volume":"93","author":"Mercier","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13633-016-0041-7","article-title":"Short stature and hypoparathyroidism in a child with Kenny-Caffey syndrome type 2 due to a novel mutation in FAM111A gene","volume":"2017","author":"Abraham","year":"2017","journal-title":"Int. J. Pediatr. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/cge.12290","article-title":"Mother-to-daughter transmission of Kenny-Caffey syndrome associated with the recurrent, dominant FAM111A mutation p.Arg569His","volume":"86","author":"Nikkel","year":"2014","journal-title":"Clin. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/ng.1104","article-title":"Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese","volume":"44","author":"Akamatsu","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1111\/cas.14483","article-title":"FAM111B enhances proliferation of KRAS-driven lung adenocarcinoma by degrading p16","volume":"111","author":"Kawasaki","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.2147\/OTT.S190934","article-title":"FAM111B, a direct target of p53, promotes the malignant process of lung adenocarcinoma","volume":"12","author":"Sun","year":"2019","journal-title":"Onco Targets Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4235","DOI":"10.1182\/blood-2007-10-119123","article-title":"An analysis of the clinical and biologic significance of TP53 loss and the identification of potential novel transcriptional targets of TP53 in multiple myeloma","volume":"112","author":"Xiong","year":"2008","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Fine, D.A., Rozenblatt-Rosen, O., Padi, M., Korkhin, A., James, R.L., Adelmant, G., Yoon, R., Guo, L., Berrios, C., and Zhang, Y. (2012). Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002949"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nie, M., Oravcov\u00e1, M., Jami-Alahmadi, Y., Wohlschlegel, J.A., Lazzerini-Denchi, E., and Boddy, M.N. (2020). Activation of FAM111A Protease Induces Defects in Nuclear Function that Likely Underlie its Roles in Disease and Viral Restriction. bioRxiv.","DOI":"10.1101\/2020.05.04.077594"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1073\/pnas.1700678114","article-title":"Triad of human cellular proteins, IRF2, FAM111A, and RFC3, restrict replication of orthopoxvirus SPI-1 host-range mutants","volume":"114","author":"Panda","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Tarnita, R.M., Wilkie, A.R., and DeCaprio, J.A. (2019). Contribution of DNA Replication to the FAM111A-Mediated Simian Virus 40 Host Range Phenotype. J. Virol., 93.","DOI":"10.1128\/JVI.01330-18"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7029","DOI":"10.1128\/JVI.00074-10","article-title":"Proteasome-dependent degradation of Daxx by the viral E1B-55K protein in human adenovirus-infected cells","volume":"84","author":"Schreiner","year":"2010","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e01782-16","DOI":"10.1128\/JVI.01782-16","article-title":"Efficient Transformation of Primary Human Mesenchymal Stromal Cells by Adenovirus Early Region 1 Oncogenes","volume":"91","author":"Speiseder","year":"2017","journal-title":"J. Virol."},{"key":"ref_16","first-page":"29","article-title":"Construction of adenovirus type 5 early region 1 and 4 virus mutants","volume":"130","author":"Groitl","year":"2007","journal-title":"Methods Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6684","DOI":"10.1073\/pnas.0702158104","article-title":"Intranuclear targeting and nuclear export of the adenovirus E1B-55K protein are regulated by SUMO1 conjugation","volume":"104","author":"Groitl","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1128\/JVI.02309-07","article-title":"Control of mRNA export by adenovirus E4orf6 and E1B55K proteins during productive infection requires E4orf6 ubiquitin ligase activity","volume":"82","author":"Blanchette","year":"2008","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9045","DOI":"10.1128\/JVI.00728-09","article-title":"A 49-kilodalton isoform of the adenovirus type 5 early region 1B 55-kilodalton protein is sufficient to support virus replication","volume":"83","author":"Schreiner","year":"2009","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1128\/JVI.01836-15","article-title":"KAP1 Is a Host Restriction Factor That Promotes Human Adenovirus E1B-55K SUMO Modification","volume":"90","author":"Mund","year":"2016","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Freudenberger, N., Meyer, T., Groitl, P., Dobner, T., and Schreiner, S. (2018). Human Adenovirus Core Protein V Is Targeted by the Host SUMOylation Machinery To Limit Essential Viral Functions. J. Virol., 92.","DOI":"10.1128\/JVI.01451-17"},{"key":"ref_22","first-page":"313","article-title":"Identification of intranuclear structures containing the 72K DNA-binding protein of human adenovirus type 5","volume":"34","author":"Pedron","year":"1984","journal-title":"Eur. J. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.virol.2007.02.012","article-title":"The adenovirus E4orf6 E3 ubiquitin ligase complex assembles in a novel fashion","volume":"364","author":"Cheng","year":"2007","journal-title":"Virology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"211","DOI":"10.2217\/fmb.11.153","article-title":"Adenovirus degradation of cellular proteins","volume":"7","author":"Schreiner","year":"2012","journal-title":"Future Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9619","DOI":"10.1128\/MCB.24.21.9619-9629.2004","article-title":"Both BC-box motifs of adenovirus protein E4orf6 are required to efficiently assemble an E3 ligase complex that degrades p53","volume":"24","author":"Blanchette","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6232","DOI":"10.1128\/JVI.00384-13","article-title":"Role of E1B55K in E4orf6\/E1B55K E3 ligase complexes formed by different human adenovirus serotypes","volume":"87","author":"Cheng","year":"2013","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1101\/gad.926401","article-title":"Degradation of p53 by adenovirus E4orf6 and E1B55K proteins occurs via a novel mechanism involving a Cullin-containing complex","volume":"15","author":"Querido","year":"2001","journal-title":"Genes Dev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8841","DOI":"10.1128\/JVI.00539-11","article-title":"Adenovirus E1A directly targets the E2F\/DP-1 complex","volume":"85","author":"Pelka","year":"2011","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1093\/nar\/gkn1057","article-title":"Transcriptional control by adenovirus E1A conserved region 3 via p300\/CBP","volume":"37","author":"Pelka","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rouillard, A.D., Gundersen, G.W., Fernandez, N.F., Wang, Z., Monteiro, C.D., McDermott, M.G., and Ma\u2019ayan, A. (2016). The harmonizome: A collection of processed datasets gathered to serve and mine knowledge about genes and proteins. Database, 2016.","DOI":"10.1093\/database\/baw100"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/6\/1015\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:09:57Z","timestamp":1760162997000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/6\/1015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,28]]},"references-count":30,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["v13061015"],"URL":"https:\/\/doi.org\/10.3390\/v13061015","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2021,5,28]]}}}