{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tomiyasu H"],"funding":["Canon Medical Systems Corporation Tokyo CL Square","Japan Science and Technology Agency Fusion Oriented REsearch for disruptive Science and Technology","Japan Society for the Promotion of Science"],"pagination":["107209"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11021968"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["300(4)"],"pubmed_abstract":["FOXO1 is a transcription factor and potential tumor suppressor that is negatively regulated downstream of PI3K-PKB/AKT signaling. Paradoxically, FOXO also promotes tumor growth, but the detailed mechanisms behind this role of FOXO are not fully understood. In this study, we revealed a molecular cascade by which the Thr24 residue of FOXO1 is phosphorylated by AKT and is dephosphorylated by calcineurin, which is a Ca<sup>2+</sup>-dependent protein phosphatase. Curiously, single nucleotide somatic mutations of FOXO1 in cancer occur frequently at and near Thr24. Using a calcineurin inhibitor and shRNA directed against calcineurin, we revealed that calcineurin-mediated dephosphorylation of Thr24 regulates FOXO1 protein stability. We also found that FOXO1 binds to the promoter region of MDM2 and"],"journal":["The Journal of biological chemistry"],"pubmed_title":["FOXO1 promotes cancer cell growth through MDM2-mediated p53 degradation."],"pmcid":["PMC11021968"],"funding_grant_id":["S22-0047","20K21503","21H02403","JPMJFR2065"],"pubmed_authors":["Hanaki S","Tomiyasu H","Habara M","Shimada M","Sato Y","Miki Y"],"additional_accession":[]},"is_claimable":false,"name":"FOXO1 promotes cancer cell growth through MDM2-mediated p53 degradation.","description":"FOXO1 is a transcription factor and potential tumor suppressor that is negatively regulated downstream of PI3K-PKB/AKT signaling. Paradoxically, FOXO also promotes tumor growth, but the detailed mechanisms behind this role of FOXO are not fully understood. In this study, we revealed a molecular cascade by which the Thr24 residue of FOXO1 is phosphorylated by AKT and is dephosphorylated by calcineurin, which is a Ca<sup>2+</sup>-dependent protein phosphatase. Curiously, single nucleotide somatic mutations of FOXO1 in cancer occur frequently at and near Thr24. Using a calcineurin inhibitor and shRNA directed against calcineurin, we revealed that calcineurin-mediated dephosphorylation of Thr24 regulates FOXO1 protein stability. We also found that FOXO1 binds to the promoter region of MDM2 and","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-06-01T18:59:36.476Z","creation":"2026-05-19T03:07:01.518Z"},"accession":"S-EPMC11021968","cross_references":{"pubmed":["38519029"],"doi":["10.1016/j.jbc.2024.107209"]}}