{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li X"],"funding":["NIAID NIH HHS","NCI NIH HHS"],"pagination":["663-75"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3135352"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["208(4)"],"pubmed_abstract":["The NOTCH1 signaling pathway is a critical determinant of cell fate decisions and drives oncogenesis through mechanisms that are incompletely understood. Using an established mouse model of T cell acute lymphoblastic leukemia (T-ALL), here we report that induction of intracellular Notch1 (ICN1) leads to repression of miR-451 and miR-709. ICN1 decreases expression of these miRNAs by inducing degradation of the E2a tumor suppressor, which transcriptionally activates the genes encoding miR-451 and miR-709. Both miR-451 and miR-709 directly repress Myc expression. In addition, miR-709 directly represses expression of the Akt and Ras-GRF1 oncogenes. We also show that repression of miR-451 and miR-709 expression is required for initiation and maintenance of mouse T-ALL. miR-451 but not miR-709 i"],"journal":["The Journal of experimental medicine"],"pubmed_title":["Repression of tumor suppressor miR-451 is essential for NOTCH1-induced oncogenesis in T-ALL."],"pmcid":["PMC3135352"],"funding_grant_id":["P30 AI060354","5P01CA109901","P01 CA068484","5P01CA68484","P01 CA109901"],"pubmed_authors":["Li X","Look AT","von Boehmer H","Sanda T","Novina CD"],"additional_accession":[]},"is_claimable":false,"name":"Repression of tumor suppressor miR-451 is essential for NOTCH1-induced oncogenesis in T-ALL.","description":"The NOTCH1 signaling pathway is a critical determinant of cell fate decisions and drives oncogenesis through mechanisms that are incompletely understood. Using an established mouse model of T cell acute lymphoblastic leukemia (T-ALL), here we report that induction of intracellular Notch1 (ICN1) leads to repression of miR-451 and miR-709. ICN1 decreases expression of these miRNAs by inducing degradation of the E2a tumor suppressor, which transcriptionally activates the genes encoding miR-451 and miR-709. Both miR-451 and miR-709 directly repress Myc expression. In addition, miR-709 directly represses expression of the Akt and Ras-GRF1 oncogenes. We also show that repression of miR-451 and miR-709 expression is required for initiation and maintenance of mouse T-ALL. miR-451 but not miR-709 i","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Apr","modification":"2025-04-22T20:37:50.68Z","creation":"2019-03-27T03:07:01Z"},"accession":"S-EPMC3135352","cross_references":{"pubmed":["21464222"],"doi":["10.1084/jem.20102384"]}}