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.
MeSH terms
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Animals
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Apoptosis Regulatory Proteins
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Carrier Proteins / genetics
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Cell Division / genetics
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Cell Transformation, Neoplastic / genetics*
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / genetics
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DNA-Binding Proteins / genetics
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Humans
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Intracellular Signaling Peptides and Proteins
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Mitochondrial Proteins / genetics
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Nerve Tissue Proteins / genetics
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Phosphatidylinositol 3-Kinases / genetics
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Signal Transduction / genetics*
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Transcription Factors / genetics*
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Transforming Growth Factor beta / genetics
Substances
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Apoptosis Regulatory Proteins
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CDKN1A protein, human
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Carrier Proteins
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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DIABLO protein, human
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DNA-Binding Proteins
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Foxd1 protein, mouse
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Foxo1 protein, mouse
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Intracellular Signaling Peptides and Proteins
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Mitochondrial Proteins
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Nerve Tissue Proteins
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Transcription Factors
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Transforming Growth Factor beta