{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:37:38Z","timestamp":1790743058207,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1010335","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T00:00:00Z","timestamp":1661212800000}}],"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1715822"],"award-info":[{"award-number":["1715822"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2114950"],"award-info":[{"award-number":["2114950"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA178974"],"award-info":[{"award-number":["CA178974"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB 1074\/A03, SFB1506\/A05, OS 287\/4-1 and GRK 2254\/C4"],"award-info":[{"award-number":["SFB 1074\/A03, SFB1506\/A05, OS 287\/4-1 and GRK 2254\/C4"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70114289"],"award-info":[{"award-number":["70114289"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["TRR81-A12 and BO1639\/9-1"],"award-info":[{"award-number":["TRR81-A12 and BO1639\/9-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"State of Hesse"},{"name":"the von Behring-R\u00f6ntgen Stiftung","award":["65-0004"],"award-info":[{"award-number":["65-0004"]}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Notch signaling is a conserved pathway that converts extracellular receptor-ligand interactions into changes in gene expression via a single transcription factor (CBF1\/RBPJ in mammals; Su(H) in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    ). In humans, RBPJ variants have been linked to Adams-Oliver syndrome (AOS), a rare autosomal dominant disorder characterized by scalp, cranium, and limb defects. Here, we found that a previously described\n                    <jats:italic>Drosophila Su(H)<\/jats:italic>\n                    allele encodes a missense mutation that alters an analogous residue found in an AOS-associated RBPJ variant. Importantly, genetic studies support a model that heterozygous\n                    <jats:italic>Drosophila<\/jats:italic>\n                    with the AOS-like\n                    <jats:italic>Su(H)<\/jats:italic>\n                    allele behave in an opposing manner to heterozygous flies with a\n                    <jats:italic>Su(H)<\/jats:italic>\n                    null allele, due to a dominant activity of sequestering either the Notch co-activator or the antagonistic Hairless co-repressor. Consistent with this model, AOS-like Su(H) and Rbpj variants have decreased DNA binding activity compared to wild type proteins, but these variants do not significantly alter protein binding to the Notch co-activator or the fly and mammalian co-repressors, respectively. Taken together, these data suggest a cofactor sequestration mechanism underlies AOS phenotypes associated with RBPJ variants, whereby the AOS-associated\n                    <jats:italic>RBPJ<\/jats:italic>\n                    allele encodes a protein with compromised DNA binding activity that retains cofactor binding, resulting in Notch target gene dysregulation.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1010335","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T13:48:26Z","timestamp":1660225706000},"page":"e1010335","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["A Drosophila Su(H) model of Adams-Oliver Syndrome reveals cofactor titration as a mechanism underlying developmental defects"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7270-6254","authenticated-orcid":true,"given":"Ellen K.","family":"Gagliani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8583-8328","authenticated-orcid":true,"given":"Lisa M.","family":"Gutzwiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1509-3620","authenticated-orcid":true,"given":"Yi","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3966-5475","authenticated-orcid":true,"given":"Yoshinobu","family":"Odaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6065-4290","authenticated-orcid":true,"given":"Phillipp","family":"Hoffmeister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Hauff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4386-1180","authenticated-orcid":true,"given":"Aleksandra","family":"Turkiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0810-8596","authenticated-orcid":true,"given":"Emily","family":"Harding-Theobald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9770-727X","authenticated-orcid":true,"given":"Patrick J.","family":"Dolph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman","family":"Borggrefe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2923-5765","authenticated-orcid":true,"given":"Franz","family":"Oswald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9791-9061","authenticated-orcid":true,"given":"Brian","family":"Gebelein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0520-1613","authenticated-orcid":true,"given":"Rhett A.","family":"Kovall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"issue":"3","key":"pgen.1010335.ref001","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.devcel.2017.04.001","article-title":"The Canonical Notch Signaling Pathway: Structural and Biochemical Insights into Shape, Sugar, and Force","volume":"41","author":"RA Kovall","year":"2017","journal-title":"Dev Cell"},{"issue":"11","key":"pgen.1010335.ref002","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nrm.2016.94","article-title":"Notch signalling in context","volume":"17","author":"SJ Bray","year":"2016","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"Pt 10","key":"pgen.1010335.ref003","first-page":"2135","article-title":"Notch signaling at a glance","volume":"126","author":"K Hori","year":"2013","journal-title":"J Cell Sci"},{"issue":"4","key":"pgen.1010335.ref004","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1152\/physrev.00005.2017","article-title":"Notch Signaling in Development, Tissue Homeostasis, and","volume":"97","author":"C Siebel","year":"2017","journal-title":"Disease. 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