title: FoxO: linking new signaling pathways.
abstract: 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.
authors.affiliation: Ludwig Institute for Cancer Research and University of California San Diego School of Medicine, San Diego, CA, USA.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Arden
mesh_terms: 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
chemical_list: 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