FIG 8.

Schematic representation of mTORC-Bach2 cascade in pre-B and mature B cells. Signaling from receptor couples to mTORCs, and Bach2 is regulated under each mTORC1 and mTORC2 at the protein level and transcript level, respectively. mTORC1 mediates Bach2 phosphorylation of serine at 535, which promotes cytoplasmic retention and degradation of Bach2 protein. FoxO1, which is negatively regulated by mTORC2, directly activates Bach2 expression. Therefore, attenuation of receptor signaling reduces mTOR activity, and it enables Bach2 to control the cell cycle by targeting specific genes, such as Ccnd3. Our data suggest that the mTOR-Bach2 cascade functions in pre-B cells with IL-7R and in mature B cells with BCR.