Forkhead Domains

Eckhard Kaufmann, University of Ulm, Ulm, Germany
Walter Knöchel, University of Ulm, Ulm, Germany

Published online: September 2005

DOI: 10.1038/npg.els.0005052

The forkhead domain or box represents an evolutionarily conserved DNA-binding motif of winged helix structure that has a degree of similarity to the helix–turn–helix motif found in other DNA-binding proteins. Forkhead box (Fox) proteins are involved in a variety of biological processes such as early embryogenesis, organogenesis, tumorigenesis and signal transduction.

Keywords: transcription factors; gene regulation; DNA–protein interaction; embryogenesis; signal transduction; tumorigenesis

Figure 1. Structure and scheme of the forkhead/winged helix domain of HNF-3 (FoxA3). Structural data are from Clark et al., (1993). Note that the forkhead domain comprises three -helices (H1, H2 and H3), three -strands (S1, S2 and S3), two wings (W1 and W2) and a turn-like structure (T¢). Main deoxyribonucleic acid (DNA) contacts are formed by H3, located within the major groove. C: carboxy-terminus; N: amino-terminus.
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 References
    Ang SL and Rossant J (1994) HNF-3 is essential for node and notochord formation in mouse development. Cell 78: 561–574.
    Chen X, Weisberg E, Fridmacher V, et al. (1997) Smad4 and FAST-1 in the assembly of activin-responsive factor. Nature 389: 85–89.
    Cirillo LA, McPherson CE, Bossard P, et al. (1998) Binding of the winged-helix transcription factor HNF3 to a linker histone site on the nucleosome. EMBO Journal 17: 244–254.
    Clark KL, Halay ED, Lai E and Burley SK (1993) Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5. Nature 36: 412–420.
    Kaestner KH, Knöchel W and Martinez DE (2000) Unified nomenclature for the winged helix/forkhead transcription factors. Genes and Development 14: 142–146.
    Kaufmann E and Knöchel W (1996) Five years on the wings of fork head. Mechanisms of Development 57: 3–20.
    Koranda M, Schleiffer A, Endler L and Ammerer G (2000) Forkhead-like transcription factors recruit Ndd1 to the chromatin of G2/M-specific promoters. Nature 406: 94–98.
    Marsden I, Jin C and Liao X (1998) Structural changes in the region directly adjacent to the DNA-binding helix highlight a possible mechanism to explain the observed changes in the sequence-specific binding of winged helix proteins. Journal of Molecular Biology 278: 293–299.
    Ogg S, Paradis S, Gottlieb S, et al. (1997) The fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389: 994–999.
    Pierrou S, Hellqvist M, Samuelsson L, Enerbäck S and Carlsson P (1994) Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending. EMBO Journal 1354: 5002–5012.
    Weigel D and Jäckle H (1990) The fork head domain: a novel DNA binding motif of eukaryotic transcription factors? Cell 63: 455–456.
 Further Reading
    Anderson MJ, Viars CS, Czekay S, Cavenee WK and Arden KC (1998) Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily. Genomics 47: 187–199.
    Brennan RG (1993) The winged-helix DNA-binding motif: another helix–turn–helix takeoff. Cell 74: 773–776.
    Brunet A, Bonni A, Zigmond MJ, et al. (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96: 857–868.
    Gajiwala KS, Chen H, Cornille F, et al. (2000) Structure of the winged-helix protein hRFX1 reveals a new mode of DNA binding. Nature 403: 916–921.
    Hatini V, Huh SO, Herzlinger D, Soares VC and Lai E (1996) Essential role of stromal mesenchyme in kidney morphogenesis revealed by targeted disruption of Winged Helix transcription factor BF-2. Genes and Development 10: 1467–1478.
    Kaestner KH, Katz J, Liu Y, Drucker DJ and Schütz G (1999) Inactivation of the winged helix transcription factor HNF3 affects glucose homeostasis and islet glucagon gene expression in vivo. Genes and Development 13: 495–504.
    Kume T, Deng K and Hogan BL (2000) Minimal phenotype of mice homozygous for a null mutation in the forkhead/winged helix gene, Mf2. Molecular and Cellular Biology 20: 1419–1425.
    Murakami S, Tedesco PM, Cypser JR and Johnson TE (2000) Molecular genetic mechanisms of life span manipulation in Caenorhabditis elegans. Annals of the New York Academy of Sciences 908: 40–49.
    Overdier DG, Porcella A and Costa RH (1994) The DNA-binding specificity of the hepatocyte nuclear factor 3/forkhead domain is influenced by amino-acid residues adjacent to the recognition helix. Molecular and Cellular Biology 14: 2755–2766.
    Xuan S, Baptista CA, Balas G, et al. (1995) Winged helix transcription factor BF-1 is essential for the development of the cerebral hemispheres. Neuron 14: 1141–1152.
 Web Links
    ePath forkhead box A2 (FOXA2); LocusID: 3170. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3170
    ePath forkhead box C1 (FOXC1); LocusID: 2296. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2296
    ePath forkhead box E1 (FOXE1); LocusID: 2304. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2304
    ePath forkhead box O1A (FOXO1a); LocusID: 2308. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2308
    ePath paired box gene 3 (PAX3); LocusID: 5077. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5077
    ePath forkhead box A2 (FOXA2); MIM number: 600288. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600288
    ePath forkhead box C1 (FOXC1); MIM number: 601090. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601090
    ePath forkhead box E1 (FOXE1); MIM number: 602617. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602617
    ePath forkhead box O1A (FOXO1a); MIM number: 136533. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?136533
    ePath paired box gene 3 (PAX3); MIM number: 193500. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?193500

Related Sub-Topics:

Intracellular and Extracellular Signalling | Cell Biology of Cancer | Cell Cycle | Signal Transduction | Protein Structure | Transcription | Genes, Molecules and Cellular Processes | Organogenesis | Cell Differentiation and Stem Cells
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Article Title: Forkhead Domains
 
How to Cite close
Kaufmann, Eckhard, and Knöchel, Walter(Sep 2005) Forkhead Domains. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005052]