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Blood. 2004 Aug 1;104(3):784-7. Epub 2004 Apr 6.

Optimal B-cell proliferation requires phosphoinositide 3-kinase-dependent inactivation of FOXO transcription factors.

Author information

  • 1Department of Molecular Biology and Biochemistry, University of California, Irvine, 92697-3900, USA.

Abstract

Transcription factors of the Forkhead Box, class O (FOXO) family promote cell-cycle arrest and/or apoptosis in a variety of cell types. Mitogenic stimuli inactivate FOXO function by way of an evolutionarily conserved pathway involving the activation of phosphoinositide 3-kinase (PI3K) and its downstream effector, Akt. Although PI3K activation is required for B-lymphocyte proliferation, it is not known whether PI3K-dependent inactivation of FOXO proteins is important for cell-cycle progression and survival of these cells. Here, we show that B-cell receptor (BCR) engagement triggers PI3K-dependent phosphorylation and nuclear export of FOXO1. Furthermore, forced expression of PI3K-independent variants of FOXO1 or FOXO3a in activated B cells induces partial arrest in G1 phase of the cell cycle and increases apoptosis. These findings establish that FOXO inactivation is a functionally important consequence of PI3K signaling in primary B cells.

PMID:
15069012
[PubMed - indexed for MEDLINE]
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