FKHR (FOXO1a) is required for myotube fusion of primary mouse myoblasts

Bois, Philippe R.J.; Grosveld, Gerard

doi:10.1093/emboj/cdg116

Cited by 153 publications

(160 citation statements)

References 38 publications

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“…As FOXO factors play a pivotal role in cell fate decisions by keeping cells in check by inhibiting cell proliferation and promoting cell death, disruption of their function leads to evasion of normal limitation on cell proliferation and transformation . Indeed, immunoblots indicate that ARMS tumor and tumor cell lines harboring the PAX3-FOXO1 fusion gene do not express FOXO1 (Bois and Grosveld, 2003). Recent findings suggest that the two models are not mutually exclusive and both may contribute to tumorigenesis.…”

Section: Foxo In Cancermentioning

confidence: 99%

FOXOs, cancer and regulation of apoptosis

2008

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Forkhead box O (FOXO) transcription factors are involved in multiple signaling pathways and play critical roles in a number of physiological and pathological processes including cancer. The importance of FOXO factors ascribes them under multiple levels of regulation including phosphorylation, acetylation/deacetylation, ubiquitination and protein-protein interactions. As FOXO factors play a pivotal role in cell fate decision, mounting evidence suggests that FOXO factors function as tumor suppressors in a variety of cancers. FOXOs are actively involved in promoting apoptosis in a mitochondriaindependent and -dependent manner by inducing the expression of death receptor ligands, including Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand, and Bcl-2 family members, such as Bim, bNIP3 and Bcl-X L , respectively. An understanding of FOXO proteins and their biology will provide new opportunities for developing more effective therapeutic approaches to treat cancer.

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Section: Foxo In Cancermentioning

confidence: 99%

FOXOs, cancer and regulation of apoptosis

2008

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“…3 In addition, Foxo-1 has been shown to stimulate fusion of primary mouse myoblasts to myotube and regulate various cellular functions, including cell cycle and apoptosis. [4][5][6][7][8] Another recently identified factor, GDF-8 or myostatin, has been characterized as an important and potent negative regulator of skeletal muscle growth and inhibitor of myoblast proliferation that belongs to the TGF-b family of secreted growth and differentiation factors. Mutations in the GDF-8 gene showed a marked increase in body weight and muscle mass in cattle.…”

Section: Introductionmentioning

confidence: 99%

Effect of RNA oligonucleotide targeting Foxo-1 on muscle growth in normal and cancer cachexia mice

Yang

Liu

et al. 2007

Cancer Gene Ther

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Foxo-1, a member of the Foxo forkhead type transcription factors, is markedly upregulated in skeletal muscle in energy-deprived states such as fasting, cancer and severe diabetes. In this study, we target the Foxo-1 mRNA in a mouse skeletal myoblast cell line C2C12 and in vivo models of normal and cancer cachexia mice by a Foxo-1 specific RNA oligonucleotide. Our results demonstrate that the RNA oligonucleotide can reduce the expression of Foxo-1 in cells and in normal and cachectic mice, leading to an increase in skeletal muscle mass of the mice. In search for the possible downstream target genes of Foxo-1, we show that when Foxo-1 expression is blocked both in cells and in mice, the level of MyoD, a myogenic factor, is increased while a muscle negative regulator GDF-8 or myostatin is suppressed. Taken together, these results show that Foxo-1 pays a critical role in development of muscle atrophy, and suggest that Foxo-1 is a potential molecular target for treatment of muscle wasting conditions.

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“…The role of FOXO transcription factors in differentiation is less well understood and is cell type dependent. In adipocytes, FOXOs inhibit differentiation most likely through induction of p21, while FOXO activation induces erythroid differentiation through induction of BTG and is required for myoblast differentiation (4,6,50). Finally, induction of Mn-superoxide dismutase and catalase by FOXO is involved in detoxification of reactive oxygen species (19,34).…”

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confidence: 99%

Induction of Mxi1-SRα by FOXO3a Contributes to Repression of Myc-Dependent Gene Expression

Delpuech

Griffiths

East³

et al. 2007

Molecular and Cellular Biology

159

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Forkhead transcription factors of the O class (FOXOs) belong to a family of transcription factors that are characterized by their conserved DNA binding domain (forkhead box). Daf-16, the FOXO orthologue in Caenorhabditis elegans, has been identified as a target of insulin-like signaling through the Daf-2/AGE-1 pathway and is involved in formation of the Dauer stage (40,53). The FOXO subgroup in mammals consists of four members, FOXO1, FOXO3a, and FOXO4 (previously termed FKHR, FKHRL1, and AFX, respectively) and FOXO6 (7,24,33,62).FOXO transcription factors bind to DNA as monomers through their winged-helix domain at a consensus motif termed DBE (for Daf-16 family member binding element) with the core sequence TTGTTAC (23). A number of FOXO target genes have been identified so far (for review, see reference 28). FOXO target genes are involved in cell cycle arrest, apoptosis, metabolism, differentiation, and the stress response. It has been shown that FOXOs induce G 1 arrest through expression of p27 KIP1 and p130 (36,46,51) and increase the duration of the G 2 phase of the cell cycle by inducing cyclin G 2 (43). In lymphocytes, FOXO activation induces cell death through induction of Bim, Trail, and Fas ligand (9,48,66). Upregulation of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase by FOXOs results in induction of gluconeogenesis (5, 30). The role of FOXO transcription factors in differentiation is less well understood and is cell type dependent. In adipocytes, FOXOs inhibit differentiation most likely through induction of p21, while FOXO activation induces erythroid differentiation through induction of BTG and is required for myoblast differentiation (4, 6, 50). Finally, induction of Mn-superoxide dismutase and catalase by FOXO is involved in detoxification of reactive oxygen species (19,34).Mammalian FOXO transcription factors are regulated through the phosphatidylinositol 3-kinase (PI3-kinase) pathway. In the absence of growth factors, FOXOs are localized to the nucleus and transcriptionally active. Activation of Akt or SGK in response to growth factor stimulation induces phosphorylation of FOXO transcription factors at three highly conserved serine and threonine residues (9, 35). As a result, FOXO transcription factors translocate to the cytoplasm. Phos-* Corresponding author. Mailing address: Gene

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FKHR (FOXO1a) is required for myotube fusion of primary mouse myoblasts

Cited by 153 publications

References 38 publications

FOXOs, cancer and regulation of apoptosis

FOXOs, cancer and regulation of apoptosis

Effect of RNA oligonucleotide targeting Foxo-1 on muscle growth in normal and cancer cachexia mice

Induction of Mxi1-SRα by FOXO3a Contributes to Repression of Myc-Dependent Gene Expression

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