Notch activation is an early and critical event during T-Cell leukemogenesis in Ikaros-deficient mice.
Mol Cell Biol
; 26(1): 209-20, 2006 Jan.
Article
en En
| MEDLINE
| ID: mdl-16354692
ABSTRACT
The Ikaros transcription factor is both a key regulator of lymphocyte differentiation and a tumor suppressor in T lymphocytes. Mice carrying a hypomorphic mutation (Ik(L/L)) in the Ikaros gene all develop thymic lymphomas. Ik(L/L) tumors always exhibit strong activation of the Notch pathway, which is required for tumor cell proliferation in vitro. Notch activation occurs early in tumorigenesis and may precede transformation, as ectopic expression of the Notch targets Hes-1 and Deltex-1 is detected in thymocytes from young Ik(L/L) mice with no overt signs of transformation. Notch activation is further amplified by secondary mutations that lead to C-terminal truncations of Notch 1. Strikingly, restoration of Ikaros activity in tumor cells leads to a rapid and specific downregulation of Notch target gene expression and proliferation arrest. Furthermore, Ikaros binds to the Notch-responsive element in the Hes-1 promoter and represses Notch-dependent transcription from this promoter. Thus, Ikaros-mediated repression of Notch target gene expression may play a critical role in defining the tumor suppressor function of this factor.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfoma de Células T
/
Proteínas de Homeodominio
/
Elementos de Respuesta
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
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Factor de Transcripción Ikaros
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Receptor Notch1
Límite:
Animals
Idioma:
En
Revista:
Mol Cell Biol
Año:
2006
Tipo del documento:
Article
País de afiliación:
Francia