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BoggleFOXO3
From Wikipedia, the free encyclopedia
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Forkhead box O3, also known as FOXO3 or FOXO3a, is a human protein encoded by the FOXO3 gene.[1]
Contents |
Function
FOXO3 belongs to the O subclass of the forkhead family of transcription factors which are characterized by a distinct fork head DNA binding domain. There are three other FoxO family members in humans, FOXO1, FOXO4 and FOXO6. These transcription factors share the ability to be inhibited and translocated out of the nucleus (aside from FOXO6, which may be constitutively nuclear) on phosphorylation by proteins such as Akt/PKB in the PI3K signalling pathway.[2] Other post-translational modifications including acetylation and methylation are seen and can result in increased or altered FOXO3a activity.
This protein likely functions as a trigger for apoptosis through upregulation of genes necessary for cell death, such as Bim and PUMA[3] , or downregulation of anti-apoptotic proteins such as FLIP.[4]
FOXO3a is also involved in protection from oxidative stress by upregulating antioxidants such as catalase and MnSOD.
Clinical significance
Deregulation of FOXO3a is involved in tumorigenesis,[5] for example translocation of this gene with the MLL gene is associated with secondary acute leukemia. Downregulation of FOXO3a activity is often seen in cancer (eg by increase in Akt activity resulting from loss of PTEN). FOXO3 is known as a tumour suppressor.
Alternatively spliced transcript variants encoding the same protein have been observed.[6]
Association with longevity
A variant of FOXO3 has been shown to be associated with longevity in humans. It is found in most centenarians across a variety of ethnic groups around the world.[7][8]
See also
References
- ^ Anderson MJ, Viars CS, Czekay S, Cavenee WK, Arden KC (January 1998). [Expression error: Missing operand for > "Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily"]. Genomics 47 (2): 187–99. doi:. PMID 9479491.
- ^ Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME (March 1999). [Expression error: Missing operand for > "Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor"]. Cell 96 (6): 857–68. doi:. PMID 10102273.
- ^ Ekoff M, Kaufmann T, Engström M, Motoyama N, Villunger A, Jönsson JI, Strasser A, Nilsson G (November 2007). [Expression error: Missing operand for > "The BH3-only protein Puma plays an essential role in cytokine deprivation induced apoptosis of mast cells"]. Blood 110 (9): 3209–17. doi:. PMID 17634411.
- ^ Skurk C, Maatz H, Kim HS, Yang J, Abid MR, Aird WC, Walsh K (January 2004). [Expression error: Missing operand for > "The Akt-regulated forkhead transcription factor FOXO3a controls endothelial cell viability through modulation of the caspase-8 inhibitor FLIP"]. The Journal of biological chemistry 279 (2): 1513–25. doi:. PMID 14551207.
- ^ Myatt SS, Lam EW (November 2007). [Expression error: Missing operand for > "The emerging roles of forkhead box (Fox) proteins in cancer"]. Nat. Rev. Cancer 7 (11): 847–59. doi:. PMID 17943136.
- ^ "Entrez Gene: FOXO3A forkhead box O3A". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2309.
- ^ Willcox BJ, Donlon TA, He Q, Chen R, Grove JS, Yano K, Masaki KH, Willcox DC, Rodriguez B, Curb JD (September 2008). [Expression error: Missing operand for > "FOXO3A genotype is strongly associated with human longevity"]. Proc. Natl. Acad. Sci. U.S.A. 105 (37): 13987–92. doi:. PMID 18765803.
- ^ Flachsbart F, Caliebe A, Kleindorp R, Blanché H, von Eller-Eberstein H, Nikolaus S, Schreiber S, Nebel A (February 2009). [Expression error: Missing operand for > "Association of FOXO3A variation with human longevity confirmed in German centenarians"]. Proc. Natl. Acad. Sci. U.S.A.. doi:. PMID 19196970.
Further reading
- Stahl M, et al. (2002). [Expression error: Missing operand for > "The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim in response to IL-2."]. J. Immunol 168: 5024–5031. PMID 11994454.
- Kino T, Chrousos GP (2004). [Expression error: Missing operand for > "Human immunodeficiency virus type-1 accessory protein Vpr: a causative agent of the AIDS-related insulin resistance/lipodystrophy syndrome?"]. Ann. N. Y. Acad. Sci. 1024: 153–67. doi:. PMID 15265780.
- Hillion J, Le Coniat M, Jonveaux P, et al. (1997). [Expression error: Missing operand for > "AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily."]. Blood 90 (9): 3714–9. PMID 9345057.
- Anderson MJ, Viars CS, Czekay S, et al. (1998). [Expression error: Missing operand for > "Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily."]. Genomics 47 (2): 187–99. doi:. PMID 9479491.
- DaSilva L, Kirken RA, Taub DD, et al. (1998). [Expression error: Missing operand for > "Molecular cloning of FKHRL1P2, a member of the developmentally regulated fork head domain transcription factor family."]. Gene 221 (1): 135–42. PMID 9852958.
- Brunet A, Bonni A, Zigmond MJ, et al. (1999). [Expression error: Missing operand for > "Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor."]. Cell 96 (6): 857–68. PMID 10102273.
- Medema RH, Kops GJ, Bos JL, Burgering BM (2000). [Expression error: Missing operand for > "AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1."]. Nature 404 (6779): 782–7. doi:. PMID 10783894.
- Brunet A, Park J, Tran H, et al. (2001). [Expression error: Missing operand for > "Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a)."]. Mol. Cell. Biol. 21 (3): 952–65. doi:. PMID 11154281.
- Schuur ER, Loktev AV, Sharma M, et al. (2001). [Expression error: Missing operand for > "Ligand-dependent interaction of estrogen receptor-alpha with members of the forkhead transcription factor family."]. J. Biol. Chem. 276 (36): 33554–60. doi:. PMID 11435445.
- Kops GJ, Medema RH, Glassford J, et al. (2002). [Expression error: Missing operand for > "Control of cell cycle exit and entry by protein kinase B-regulated forkhead transcription factors."]. Mol. Cell. Biol. 22 (7): 2025–36. PMID 11884591.
- Mahmud DL, G-Amlak M, Deb DK, et al. (2002). [Expression error: Missing operand for > "Phosphorylation of forkhead transcription factors by erythropoietin and stem cell factor prevents acetylation and their interaction with coactivator p300 in erythroid progenitor cells."]. Oncogene 21 (10): 1556–62. doi:. PMID 11896584.
- Nadal A, Marrero PF, Haro D (2002). [Expression error: Missing operand for > "Down-regulation of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene by insulin: the role of the forkhead transcription factor FKHRL1."]. Biochem. J. 366 (Pt 1): 289–97. doi:. PMID 12027802.
- Wistow G, Bernstein SL, Wyatt MK, et al. (2002). [Expression error: Missing operand for > "Expressed sequence tag analysis of human RPE/choroid for the NEIBank Project: over 6000 non-redundant transcripts, novel genes and splice variants."]. Mol. Vis. 8: 205–20. PMID 12107410.
- Modur V, Nagarajan R, Evers BM, Milbrandt J (2003). [Expression error: Missing operand for > "FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer."]. J. Biol. Chem. 277 (49): 47928–37. doi:. PMID 12351634.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). [Expression error: Missing operand for > "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences."]. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:. PMID 12477932.
- Charvet C, Alberti I, Luciano F, et al. (2003). [Expression error: Missing operand for > "Proteolytic regulation of Forkhead transcription factor FOXO3a by caspase-3-like proteases."]. Oncogene 22 (29): 4557–68. doi:. PMID 12881712.
- Crossley LJ (2003). [Expression error: Missing operand for > "Neutrophil activation by fMLP regulates FOXO (forkhead) transcription factors by multiple pathways, one of which includes the binding of FOXO to the survival factor Mcl-1."]. J. Leukoc. Biol. 74 (4): 583–92. doi:. PMID 12960271.
- Sunters A, Fernández de Mattos S, Stahl M, et al. (2004). [Expression error: Missing operand for > "FoxO3a transcriptional regulation of Bim controls apoptosis in paclitaxel-treated breast cancer cell lines."]. J. Biol. Chem. 278 (50): 49795–805. doi:. PMID 14527951.
- Skurk C, Maatz H, Kim HS, et al. (2004). [Expression error: Missing operand for > "The Akt-regulated forkhead transcription factor FOXO3a controls endothelial cell viability through modulation of the caspase-8 inhibitor FLIP."]. J. Biol. Chem. 279 (2): 1513–25. doi:. PMID 14551207.
- Dansen TB, Kops GJ, Denis S, et al. (2004). [Expression error: Missing operand for > "Regulation of sterol carrier protein gene expression by the forkhead transcription factor FOXO3a."]. J. Lipid Res. 45 (1): 81–8. doi:. PMID 14563822.
- Mungall AJ, Palmer SA, Sims SK, et al. (2003). [Expression error: Missing operand for > "The DNA sequence and analysis of human chromosome 6."]. Nature 425 (6960): 805–11. doi:. PMID 14574404.
External links
- MeSH FOXO3A+protein,+human
- http://www.cisreg.ca/cgi-bin/tfe/articles.pl?tfid=443 Transcription Factor encyclopedia entry for FOXO3
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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