FoxO

Two recent reports (Seoane et al. 2004Seoane, J., Le, H.-V., Shen, L., Anderson, S.A., and Massagué, J. (2004). Cell in press.Google Scholar, Hu et al. 2004Hu, L.S., Lee, D.-F., Xia, W., Golfman, L., Ou-Yang, F., Yang, J.-Y., Zou, Y., Bao, S., Hanada, N., Saso, H., et al. (2004). Cell in press.Google Scholar) reveal new roles for FoxO proteins in cell proliferation and tumorigenesis. Seoane and colleagues show that FoxO proteins play key roles in the TGFβ-dependent activation of p21Cip1 by partnering with Smad3 and Smad4. FoxG1, a protein from a distinct Fox subfamily, binds FoxO/Smad complexes and blocks p21Cip1 expression. These interactions establish a relationship between the PI3K pathway, FoxG1, and the TGFβ/Smad pathways. The second report identifies IκB kinase as a negative regulator of FoxO proteins, suggesting a mechanism for relieving negative regulation of cell cycle and promoting tumor cell proliferation.