FoxO: linking new signaling pathways.
Two recent reports reveal new roles for FoxO proteins in cell proliferation and tumorigenesis. Seoane and colleagues show that FoxO proteins play key roles in the TGFbeta-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 TGFbeta/Smad pathways. The second report identifies IkappaB kinase as a negative regulator of FoxO proteins, suggesting a mechanism for relieving negative regulation of cell cycle and promoting tumor cell proliferation.
Arden
Karen C
KC
Ludwig Institute for Cancer Research and University of California San Diego School of Medicine, San Diego, CA, USA.
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C493956:CDKN1A protein, human; C412403:DIABLO protein, human; C489562:Foxd1 protein, mouse; C467200:Foxo1 protein, mouse