{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:59:44Z","timestamp":1788998384229,"version":"build-2803163510"},"reference-count":50,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T00:00:00Z","timestamp":1616112000000},"content-version":"vor","delay-in-days":383,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Cell"],"published-print":{"date-parts":[[2020,3]]},"DOI":"10.1016\/j.molcel.2020.01.009","type":"journal-article","created":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T18:53:55Z","timestamp":1583952835000},"page":"1294-1306.e5","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":61,"title":["Genome-wide Screening Identifies SFMBT1 as an Oncogenic Driver in Cancer with VHL Loss"],"prefix":"10.1016","volume":"77","author":[{"given":"Xijuan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy M.","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibiao","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianxin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Zurlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis S.","family":"Ptacek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Herring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianming","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert S.","family":"Baldwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William Y.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc W.","family":"Kirschner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.molcel.2020.01.009_bib1","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/S0076-6879(05)99028-9","article-title":"Identification of ubiquitin ligase substrates by in\u00a0vitro expression cloning","volume":"399","author":"Ayad","year":"2005","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.molcel.2020.01.009_bib2","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1039\/c3cc00181d","article-title":"Synthesis of selective inhibitors of sphingosine kinase 1","volume":"49","author":"Baek","year":"2013","journal-title":"Chem. Commun. (Camb.)"},{"key":"10.1016\/j.molcel.2020.01.009_bib3","doi-asserted-by":"crossref","first-page":"15770","DOI":"10.1038\/ncomms15770","article-title":"MYC activation cooperates with Vhl and Ink4a\/Arf loss to induce clear cell renal cell carcinoma","volume":"8","author":"Bailey","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.molcel.2020.01.009_bib4","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/1471-2105-11-94","article-title":"Evaluation of statistical methods for normalization and differential expression in mRNA-Seq experiments","volume":"11","author":"Bullard","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.molcel.2020.01.009_bib5","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1039\/c3md00201b","article-title":"Novel sphingosine-containing analogues selectively inhibit sphingosine kinase (SK) isozymes, induce SK1 proteasomal degradation and reduce DNA synthesis in human pulmonary arterial smooth muscle cells","volume":"4","author":"Byun","year":"2013","journal-title":"MedChemComm"},{"key":"10.1016\/j.molcel.2020.01.009_bib6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nature12222","article-title":"Comprehensive molecular characterization of clear cell renal cell carcinoma","volume":"499","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.molcel.2020.01.009_bib7","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nature19796","article-title":"Targeting renal cell carcinoma with a HIF-2 antagonist","volume":"539","author":"Chen","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.molcel.2020.01.009_bib8","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nature19795","article-title":"On-Target Efficacy of a HIF2alpha Antagonist in Preclinical Kidney Cancer Models","volume":"539","author":"Cho","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.molcel.2020.01.009_bib9","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1093\/hmg\/10.10.1029","article-title":"Contrasting effects on HIF-1alpha regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel-Lindau disease","volume":"10","author":"Clifford","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.molcel.2020.01.009_bib10","doi-asserted-by":"crossref","first-page":"e46490","DOI":"10.7554\/eLife.46490","article-title":"Lack of activity of recombinant HIF prolyl hydroxylases (PHDs) on reported non-HIF substrates","volume":"8","author":"Cockman","year":"2019","journal-title":"eLife"},{"key":"10.1016\/j.molcel.2020.01.009_bib11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"10.1016\/j.molcel.2020.01.009_bib12","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.molcel.2011.11.031","article-title":"Regulation of KLF4 turnover reveals an unexpected tissue-specific role of pVHL in tumorigenesis","volume":"45","author":"Gamper","year":"2012","journal-title":"Mol. Cell"},{"key":"10.1016\/j.molcel.2020.01.009_bib13","first-page":"341","article-title":"Immune checkpoint blockade as a novel immunotherapeutic strategy for renal cell carcinoma: a review of clinical trials","volume":"18","author":"Godwin","year":"2014","journal-title":"Discov. Med."},{"key":"10.1016\/j.molcel.2020.01.009_bib14","doi-asserted-by":"crossref","first-page":"3924","DOI":"10.1182\/blood-2003-07-2535","article-title":"Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors","volume":"103","author":"Gordeuk","year":"2004","journal-title":"Blood"},{"key":"10.1016\/j.molcel.2020.01.009_bib15","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.semcdb.2005.03.006","article-title":"The VHL tumor suppressor in development and disease: functional studies in mice by conditional gene targeting","volume":"16","author":"Haase","year":"2005","journal-title":"Semin. Cell Dev. Biol."},{"key":"10.1016\/j.molcel.2020.01.009_bib16","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities","volume":"38","author":"Heinz","year":"2010","journal-title":"Mol. Cell"},{"key":"10.1016\/j.molcel.2020.01.009_bib17","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.cell.2014.06.049","article-title":"Multi-platform analysis of 12 cancer types reveals molecular classification within and across tissues-of-origin","volume":"158","author":"Hoadley","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.molcel.2020.01.009_bib18","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1093\/hmg\/10.10.1019","article-title":"von Hippel-Lindau protein mutants linked to type 2C VHL disease preserve the ability to downregulate HIF","volume":"10","author":"Hoffman","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.molcel.2020.01.009_bib19","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1126\/science.1059817","article-title":"HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing","volume":"292","author":"Ivan","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.molcel.2020.01.009_bib20","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1126\/science.1059796","article-title":"Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation","volume":"292","author":"Jaakkola","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.molcel.2020.01.009_bib21","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/nrc885","article-title":"Molecular basis of the VHL hereditary cancer syndrome","volume":"2","author":"Kaelin","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.molcel.2020.01.009_bib22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S1535-6108(02)00043-0","article-title":"Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein","volume":"1","author":"Kondo","year":"2002","journal-title":"Cancer Cell"},{"key":"10.1016\/j.molcel.2020.01.009_bib23","doi-asserted-by":"crossref","first-page":"E83","DOI":"10.1371\/journal.pbio.0000083","article-title":"Inhibition of HIF2alpha is sufficient to suppress pVHL-defective tumor growth","volume":"1","author":"Kondo","year":"2003","journal-title":"PLoS Biol."},{"key":"10.1016\/j.molcel.2020.01.009_bib24","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/nrd4099","article-title":"Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond","volume":"12","author":"Kunkel","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.molcel.2020.01.009_bib25","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.cell.2015.03.011","article-title":"A lactate-induced response to hypoxia","volume":"161","author":"Lee","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.molcel.2020.01.009_bib26","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1582-4934.2010.01238.x","article-title":"Two sides to every story: the HIF-dependent and HIF-independent functions of pVHL","volume":"15","author":"Li","year":"2011","journal-title":"J.\u00a0Cell. Mol. Med."},{"key":"10.1016\/j.molcel.2020.01.009_bib27","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.ccr.2013.10.025","article-title":"SQSTM1 is a pathogenic target of 5q copy number gains in kidney cancer","volume":"24","author":"Li","year":"2013","journal-title":"Cancer Cell"},{"key":"10.1016\/j.molcel.2020.01.009_bib28","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"10.1016\/j.molcel.2020.01.009_bib29","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet.journal"},{"key":"10.1016\/j.molcel.2020.01.009_bib30","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.jmb.2012.08.022","article-title":"Histone recognition by human malignant brain tumor domains","volume":"423","author":"Nady","year":"2012","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.molcel.2020.01.009_bib31","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.cell.2005.12.037","article-title":"Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes","volume":"124","author":"Nam","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.molcel.2020.01.009_bib32","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.molcel.2020.01.009_bib33","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.molcel.2020.01.009_bib34","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.stem.2010.08.002","article-title":"Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer","volume":"7","author":"Sauvageau","year":"2010","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.molcel.2020.01.009_bib35","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1042\/BJ20111929","article-title":"Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1","volume":"444","author":"Schnute","year":"2012","journal-title":"Biochem. J."},{"key":"10.1016\/j.molcel.2020.01.009_bib36","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.cell.2012.01.021","article-title":"Hypoxia-inducible factors in physiology and medicine","volume":"148","author":"Semenza","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.molcel.2020.01.009_bib37","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nrg3682","article-title":"Transcriptional enhancers: from properties to genome-wide predictions","volume":"15","author":"Shlyueva","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.molcel.2020.01.009_bib38","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1172\/JCI32086","article-title":"Suppression of renal cell carcinoma growth by inhibition of Notch signaling in\u00a0vitro and in\u00a0vivo","volume":"118","author":"Sj\u00f6lund","year":"2008","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.molcel.2020.01.009_bib39","doi-asserted-by":"crossref","first-page":"27680","DOI":"10.1074\/jbc.M113.482349","article-title":"The malignant brain tumor (MBT) domain protein SFMBT1 is an integral histone reader subunit of the LSD1 demethylase complex for chromatin association and epithelial-to-mesenchymal transition","volume":"288","author":"Tang","year":"2013","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.molcel.2020.01.009_bib40","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1093\/nar\/29.6.1373","article-title":"The N- and C-terminal regions of RBP-J interact with the ankyrin repeats of Notch1 RAMIC to activate transcription","volume":"29","author":"Tani","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.molcel.2020.01.009_bib41","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1016\/j.febslet.2007.06.025","article-title":"Human SFMBT is a transcriptional repressor protein that selectively binds the N-terminal tail of histone H3","volume":"581","author":"Wu","year":"2007","journal-title":"FEBS Lett."},{"key":"10.1016\/j.molcel.2020.01.009_bib42","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/S0076-6879(04)81022-X","article-title":"Analysis of von Hippel-Lindau hereditary cancer syndrome: implications of oxygen sensing","volume":"381","author":"Yang","year":"2004","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.molcel.2020.01.009_bib43","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1158\/2159-8290.CD-17-0375","article-title":"VHL Deficiency Drives Enhancer Activation of Oncogenes in Clear Cell Renal Cell Carcinoma","volume":"7","author":"Yao","year":"2017","journal-title":"Cancer Discov."},{"key":"10.1016\/j.molcel.2020.01.009_bib44","doi-asserted-by":"crossref","first-page":"E35","DOI":"10.3390\/biomedicines6010035","article-title":"VHL and Hypoxia Signaling: Beyond HIF in Cancer","volume":"6","author":"Zhang","year":"2018","journal-title":"Biomedicines"},{"key":"10.1016\/j.molcel.2020.01.009_bib45","doi-asserted-by":"crossref","first-page":"R137","DOI":"10.1186\/gb-2008-9-9-r137","article-title":"Model-based analysis of ChIP-Seq (MACS)","volume":"9","author":"Zhang","year":"2008","journal-title":"Genome Biol."},{"key":"10.1016\/j.molcel.2020.01.009_bib46","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.ccr.2009.09.029","article-title":"Control of cyclin D1 and breast tumorigenesis by the EglN2 prolyl hydroxylase","volume":"16","author":"Zhang","year":"2009","journal-title":"Cancer Cell"},{"key":"10.1016\/j.molcel.2020.01.009_bib47","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1101\/gad.210963.112","article-title":"SFMBT1 functions with LSD1 to regulate expression of canonical histone genes and chromatin-related factors","volume":"27","author":"Zhang","year":"2013","journal-title":"Genes Dev."},{"key":"10.1016\/j.molcel.2020.01.009_bib48","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1101\/gad.210963.112","article-title":"SFMBT1 functions with LSD1 to regulate expression of canonical histone genes and chromatin-related factors","volume":"27","author":"Zhang","year":"2013","journal-title":"Genes Dev."},{"key":"10.1016\/j.molcel.2020.01.009_bib49","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1158\/1078-0432.CCR-14-2031","article-title":"Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal Cancer","volume":"21","author":"Zhang","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.molcel.2020.01.009_bib50","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1126\/science.aap8411","article-title":"VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma","volume":"361","author":"Zhang","year":"2018","journal-title":"Science"}],"container-title":["Molecular Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1097276520300095?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1097276520300095?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:29:04Z","timestamp":1761092944000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1097276520300095"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3]]},"references-count":50,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["S1097276520300095"],"URL":"https:\/\/doi.org\/10.1016\/j.molcel.2020.01.009","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.737324604.793570729","asserted-by":"object"}]},"ISSN":["1097-2765"],"issn-type":[{"value":"1097-2765","type":"print"}],"subject":[],"published":{"date-parts":[[2020,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Genome-wide Screening Identifies SFMBT1 as an Oncogenic Driver in Cancer with VHL Loss","name":"articletitle","label":"Article Title"},{"value":"Molecular Cell","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.molcel.2020.01.009","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Inc.","name":"copyright","label":"Copyright"}]}}