{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:04:45Z","timestamp":1790687085163,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"3","license":[{"start":{"date-parts":[[2019,6,30]],"date-time":"2019-06-30T00:00:00Z","timestamp":1561852800000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA63113"],"award-info":[{"award-number":["R01CA63113"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA173023"],"award-info":[{"award-number":["R01CA173023"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["P01CA050661"],"award-info":[{"award-number":["P01CA050661"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["F31CA213464"],"award-info":[{"award-number":["F31CA213464"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["F31CA177274"],"award-info":[{"award-number":["F31CA177274"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wellcome Trust DBT India Alliance Early Career Fellowship","award":["IA\/E\/14\/1\/501773"],"award-info":[{"award-number":["IA\/E\/14\/1\/501773"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,1,15]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Merkel cell carcinoma (MCC) is an aggressive skin cancer. While virus-negative [Merkel cell polyomavirus (MCV)] MCC contains inactivating mutations in RB and p53, MCV-positive MCC usually contains wild-type RB and p53. We demonstrate that MCV large T antigen binding to RB results in p53 activation, while MCV small T antigen reduces p53 activation by increasing levels of MDM2 and CK1\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mi>\u03b1<\/mml:mi>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    , an activator of MDM4. Targeted degradation of CK1\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mi>\u03b1<\/mml:mi>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    by lenalidomide or a specific MDM4 inhibitor acts synergistically with MDM2 inhibitors to activate p53 and induce apoptosis. Our work uncovers the mechanism behind MCV control of p53 in MCC and demonstrates the utility of targeting MDM2 and MDM4 combinatorially in p53 wild-type tumors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1818798116","type":"journal-article","created":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T20:05:59Z","timestamp":1546286759000},"page":"1027-1032","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":95,"title":["Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 response"],"prefix":"10.1073","volume":"116","author":[{"given":"Donglim Esther","family":"Park","sequence":"first","affiliation":[{"name":"Program in Virology, Graduate School of Arts and Sciences, Harvard University, Cambridge, MA 02138;"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215;"},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Berrios","sequence":"additional","affiliation":[{"name":"Program in Virology, Graduate School of Arts and Sciences, Harvard University, Cambridge, MA 02138;"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Montero","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215;"},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115;"},{"name":"Nanobioengineering Group, Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Cort\u00e9s-Cros","sequence":"additional","affiliation":[{"name":"Disease Area Oncology, Novartis Institutes for Biomedical Research, CH-4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Ferretti","sequence":"additional","affiliation":[{"name":"Disease Area Oncology, Novartis Institutes for Biomedical Research, CH-4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reety","family":"Arora","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215;"},{"name":"National Center for Biological Sciences, Tata Institute of Fundamental Research, 560065 Bangalore, India;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Tillgren","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics Core, Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prafulla C.","family":"Gokhale","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics Core, Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0896-167X","authenticated-orcid":false,"given":"James A.","family":"DeCaprio","sequence":"additional","affiliation":[{"name":"Program in Virology, Graduate School of Arts and Sciences, Harvard University, Cambridge, MA 02138;"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215;"},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2018,12,31]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.77"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2017.10.028"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1152586"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64116"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46323"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00385-13"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02079-16"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-0702"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.02200"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/25867"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3414"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1317398110"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1420833112"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.6.11.4298"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006668"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003713"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006020"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-0215"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.87062"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.169"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14610"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16979"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-2747"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3437"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1101-973"},{"key":"e_1_3_3_26_2","first-page":"4827","article-title":"Evaluation of a soluble tetrazolium\/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines","volume":"48","author":"Scudiero D","year":"1988","unstructured":"D Scudiero, , Evaluation of a soluble tetrazolium\/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res 48, 4827\u20134833 (1988).","journal-title":"Cancer Res"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/86.20.1517"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx162"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm400487c"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm401753e"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.01.042"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(15)00050-2"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.098103"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_3_35_2","unstructured":"K Blighe Enhancedvolcano: Publication-ready volcano plots with enhanced colouring and labeling. Available at https:\/\/github.com\/kevinblighe. Accessed November 23 2018. (2018)."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1818798116","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1818798116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T03:19:25Z","timestamp":1649819965000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1818798116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,31]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,1,15]]}},"alternative-id":["10.1073\/pnas.1818798116"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1818798116","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,31]]},"assertion":[{"value":"2018-12-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}