KLF4 is a FOXO target gene that suppresses B cell proliferation.

Abstract:

: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.

journal_name

Int Immunol

journal_title

International immunology

authors

Yusuf I,Kharas MG,Chen J,Peralta RQ,Maruniak A,Sareen P,Yang VW,Kaestner KH,Fruman DA

doi

10.1093/intimm/dxn024

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

671-81

issue

5

eissn

0953-8178

issn

1460-2377

pii

dxn024

journal_volume

20

pub_type

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