{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ghosh J"],"funding":["NIDDK NIH HHS","NHLBI NIH HHS","NCI NIH HHS"],"pagination":["2621-5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4922705"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["126(7)"],"pubmed_abstract":["Hyperactivation of the mTOR pathway impairs hematopoietic stem cell (HSC) functions and promotes leukemogenesis. mTORC1 and mTORC2 differentially control normal and leukemic stem cell functions. mTORC1 regulates p70 ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E-binding (eIF4E-binding) protein 1 (4E-BP1), and mTORC2 modulates AKT activation. Given the extensive crosstalk that occurs between mTORC1 and mTORC2 signaling pathways, we assessed the role of the mTORC1 substrate S6K1 in the regulation of both normal HSC functions and in leukemogenesis driven by the mixed lineage leukemia (MLL) fusion oncogene MLL-AF9. We demonstrated that S6K1 deficiency impairs self-renewal of murine HSCs by reducing p21 expression. Loss of S6K1 also improved survival in mice transplant"],"journal":["The Journal of clinical investigation"],"pubmed_title":["S6K1 regulates hematopoietic stem cell self-renewal and leukemia maintenance."],"pmcid":["PMC4922705"],"funding_grant_id":["R01 CA173852","T32 HL007910","R01 HL075816","R01 CA134777","R01 CA168815","R01 HL081111","R01 HL077177","R01 DK097837"],"pubmed_authors":["Ma P","Carlesso N","Liu Y","Kapur R","Chan RJ","Ramdas B","Mali RS","Ghosh J","Plas DR","Chatterjee A","Kobayashi M"],"additional_accession":[]},"is_claimable":false,"name":"S6K1 regulates hematopoietic stem cell self-renewal and leukemia maintenance.","description":"Hyperactivation of the mTOR pathway impairs hematopoietic stem cell (HSC) functions and promotes leukemogenesis. mTORC1 and mTORC2 differentially control normal and leukemic stem cell functions. mTORC1 regulates p70 ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E-binding (eIF4E-binding) protein 1 (4E-BP1), and mTORC2 modulates AKT activation. Given the extensive crosstalk that occurs between mTORC1 and mTORC2 signaling pathways, we assessed the role of the mTORC1 substrate S6K1 in the regulation of both normal HSC functions and in leukemogenesis driven by the mixed lineage leukemia (MLL) fusion oncogene MLL-AF9. We demonstrated that S6K1 deficiency impairs self-renewal of murine HSCs by reducing p21 expression. Loss of S6K1 also improved survival in mice transplant","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Jul","modification":"2026-05-05T08:27:32.32Z","creation":"2026-04-07T21:35:42.681Z"},"accession":"S-EPMC4922705","cross_references":{"pubmed":["27294524"],"doi":["10.1172/jci84565","10.1172/JCI84565"]}}