KLF4 is a FOXO target gene that suppresses B cell proliferation.
Int Immunol
; 20(5): 671-81, 2008 May.
Article
en En
| MEDLINE
| ID: mdl-18375530
Lymphocytes circulate in a quiescent (G(0)) state until they encounter specific antigens. In T cells, quiescence is programmed by transcription factors of the forkhead box O (FOXO) and Krüppel-like factor (KLF) families. However, the transcription factors that regulate B cell quiescence are not known. KLF4 is a candidate tumor suppressor gene in B lymphocytes, and thus a likely candidate for regulating B cell homeostasis. Here, we show that RNA and protein expression of murine KLF4 decreases following B cell activation. Forced expression of KLF4 in proliferating B cell blasts causes a G(1) cell cycle arrest. This effect requires the DNA binding and transactivation domains of KLF4 and correlates with changes in the expression of known KLF target genes. We present evidence that Klf4 is a target gene for FOXO transcription factors, which also suppress B cell proliferation. To determine the effect of KLF4 loss-of-function, we generated mice with B cell-specific deletion of the Klf4 gene. These mice exhibited normal B cell development and function with no evidence of a lowered activation threshold. Collectively, our findings indicate that KLF4 has growth-suppressive properties in B cells but might be redundant with other members of the KLF family in maintaining B cell quiescence.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Linfocitos B
/
Proteínas de Homeodominio
/
Factores de Transcripción de Tipo Kruppel
/
Factores de Transcripción Forkhead
Límite:
Animals
Idioma:
En
Revista:
Int Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido