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http://hdl.handle.net/2445/177169
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DC Field | Value | Language |
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dc.contributor.author | González-García, Sara | - |
dc.contributor.author | García-Peydró, Marina | - |
dc.contributor.author | Martín-Gayo, Enrique | - |
dc.contributor.author | Ballestar Tarín, Esteban | - |
dc.contributor.author | Esteller, Manel | - |
dc.contributor.author | Bornstein, Rafael | - |
dc.contributor.author | Pompa, José Luis de la | - |
dc.contributor.author | Ferrando, Adolfo A. | - |
dc.contributor.author | Toribio, María L. | - |
dc.date.accessioned | 2021-05-12T13:37:37Z | - |
dc.date.available | 2021-05-12T13:37:37Z | - |
dc.date.issued | 2009-04-13 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.uri | http://hdl.handle.net/2445/177169 | - |
dc.description.abstract | Notch1 activation is essential for T-lineage specification of lymphomyeloid progenitors seeding the thymus. Progression along the T cell lineage further requires cooperative signaling provided by the interleukin 7 receptor (IL-7R), but the molecular mechanisms responsible for the dynamic and lineage-specific regulation of IL-7R during thymopoiesis are unknown. We show that active Notch1 binds to a conserved CSL-binding site in the human IL7R gene promoter and critically regulates IL7R transcription and IL-7R alpha chain (IL-7Ralpha) expression via the CSL-MAML complex. Defective Notch1 signaling selectively impaired IL-7Ralpha expression in T-lineage cells, but not B-lineage cells, and resulted in a compromised expansion of early human developing thymocytes, which was rescued upon ectopic IL-7Ralpha expression. The pathological implications of these findings are demonstrated by the regulation of IL-7Ralpha expression downstream of Notch1 in T cell leukemias. Thus, Notch1 controls early T cell development, in part by regulating the stage- and lineage-specific expression of IL-7Ralpha. | - |
dc.format.extent | 13 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Rockefeller University Press | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1084/jem.20081922 | - |
dc.relation.ispartof | Journal of Experimental Medicine, 2009, vol. 206, num. 4, p. 779-791 | - |
dc.relation.uri | https://doi.org/10.1084/jem.20081922 | - |
dc.rights | (c) Rockefeller University Press, 2009 | - |
dc.source | Articles publicats en revistes (Ciències Fisiològiques) | - |
dc.subject.classification | Expressió gènica | - |
dc.subject.classification | Leucèmia | - |
dc.subject.classification | Immunologia | - |
dc.subject.classification | Timus (Glàndula) | - |
dc.subject.other | Gene expression | - |
dc.subject.other | Leukemia | - |
dc.subject.other | Immunology | - |
dc.subject.other | Thymus | - |
dc.title | CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7R{alpha}gene expression in early human thymopoiesis and leukemia | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 700224 | - |
dc.date.updated | 2021-05-12T13:37:37Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 19349467 | - |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) |
Files in This Item:
File | Description | Size | Format | |
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700224.pdf | 4.81 MB | Adobe PDF | View/Open |
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