title: Translational initiation regulated by ATM in dendritic cells development.
abstract: Ataxia telangiectasia mutated (ATM) protein has been implicated in multiple pathways such as DNA repair, cell cycle checkpoint, cell growth, development, and stem cell renewal. In this study, we demonstrate evidence that ATM is involved in granulocyte macrophage colony-stimulating factor (GM-CSF)-induced dendritic cell (DC) development from bone marrow (BM) cells. Inactivation of ATM protein results in decreased BM proliferation, leading to reduced DC development and their activity for T cell activation. Expression of Jak2, STAT5, and mTOR is suppressed in both wild-type and ATM-null BM prior to GM-CSF stimulation. Activation of those proteins is delayed and prolonged hypophosphorylation of 4EBP1 is observed in ATM-null BM when treated with GM-CSF, although Erk and p38 are similarly expressed and activated in both wild-type and ATM-null BM cell types. Akt is also suppressed in wild-type BM, and transduction of constitutively active Akt or STAT5 in ATM-null BM restores DC development. Together, these results illustrate that ATM deficiency causes impaired initiation of protein translation in BM, leading to immature development of DC.
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: E Y
authors.initials: EY
authors.lastname: So
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: T
authors.initials: T
authors.lastname: Ouchi
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010442:Peptide Chain Initiation, Translational
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse