1l8r Citations

Structure of the retinal determination protein Dachshund reveals a DNA binding motif.

Structure 10 787-95 (2002)
Cited: 46 times
EuropePMC logo PMID: 12057194


The Dachshund proteins are essential components of a regulatory network controlling cell fate determination. They have been implicated in eye, limb, brain, and muscle development. These proteins cannot be assigned to any recognizable structural or functional class based on amino acid sequence analysis. The 1.65 A crystal structure of the most conserved domain of human DACHSHUND is reported here. The protein forms an alpha/beta structure containing a DNA binding motif similar to that found in the winged helix/forkhead subgroup of the helix-turn-helix family. This unexpected finding alters the previously proposed molecular models for the role of Dachshund in the eye determination pathway. Furthermore, it provides a rational framework for future mechanistic analyses of the Dachshund proteins in several developmental contexts.

Articles - 1l8r mentioned but not cited (5)

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Reviews citing this publication (10)

  1. The DACH/EYA/SIX gene network and its role in tumor initiation and progression. Liu Y, Han N, Zhou S, Zhou R, Yuan X, Xu H, Zhang C, Yin T, Wu K. Int. J. Cancer 138 1067-1075 (2016)
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  9. The eyes absent family of phosphotyrosine phosphatases: properties and roles in developmental regulation of transcription. Jemc J, Rebay I. Annu. Rev. Biochem. 76 513-538 (2007)
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Articles citing this publication (31)

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  4. DACH1 is a cell fate determination factor that inhibits cyclin D1 and breast tumor growth. Wu K, Li A, Rao M, Liu M, Dailey V, Yang Y, Di Vizio D, Wang C, Lisanti MP, Sauter G, Russell RG, Cvekl A, Pestell RG. Mol. Cell. Biol. 26 7116-7129 (2006)
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  6. The cell fate determination factor dachshund inhibits androgen receptor signaling and prostate cancer cellular growth. Wu K, Katiyar S, Witkiewicz A, Li A, McCue P, Song LN, Tian L, Jin M, Pestell RG. Cancer Res. 69 3347-3355 (2009)
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  8. Djeyes absent (Djeya) controls prototypic planarian eye regeneration by cooperating with the transcription factor Djsix-1. Mannini L, Rossi L, Deri P, Gremigni V, Salvetti A, Saló E, Batistoni R. Dev. Biol. 269 346-359 (2004)
  9. Epigenetic regulation of DACH1, a novel Wnt signaling component in colorectal cancer. Yan W, Wu K, Herman JG, Brock MV, Fuks F, Yang L, Zhu H, Li Y, Yang Y, Guo M. Epigenetics 8 1373-1383 (2013)
  10. Structure of the polycomb group protein PCGF1 in complex with BCOR reveals basis for binding selectivity of PCGF homologs. Junco SE, Wang R, Gaipa JC, Taylor AB, Schirf V, Gearhart MD, Bardwell VJ, Demeler B, Hart PJ, Kim CA. Structure 21 665-671 (2013)
  11. Attenuation of Forkhead signaling by the retinal determination factor DACH1. Zhou J, Wang C, Wang Z, Dampier W, Wu K, Casimiro MC, Chepelev I, Popov VM, Quong A, Tozeren A, Zhao K, Lisanti MP, Pestell RG. Proc. Natl. Acad. Sci. U.S.A. 107 6864-6869 (2010)
  12. Mutation analysis of two candidate genes for premature ovarian failure, DACH2 and POF1B. Bione S, Rizzolio F, Sala C, Ricotti R, Goegan M, Manzini MC, Battaglia R, Marozzi A, Vegetti W, Dalprà L, Crosignani PG, Ginelli E, Nappi R, Bernabini S, Bruni V, Torricelli F, Zuffardi O, Toniolo D. Hum. Reprod. 19 2759-2766 (2004)
  13. Retinal determination genes as targets and possible effectors of extracellular signals. Firth LC, Baker NE. Dev. Biol. 327 366-375 (2009)
  14. Using Drosophila to decipher how mutations associated with human branchio-oto-renal syndrome and optical defects compromise the protein tyrosine phosphatase and transcriptional functions of eyes absent. Mutsuddi M, Chaffee B, Cassidy J, Silver SJ, Tootle TL, Rebay I. Genetics 170 687-695 (2005)
  15. Crystal structure of the dachshund homology domain of human SKI. Wilson JJ, Malakhova M, Zhang R, Joachimiak A, Hegde RS. Structure 12 785-792 (2004)
  16. Epigenetic silencing of DACH1 induces the invasion and metastasis of gastric cancer by activating TGF-β signalling. Yan W, Wu K, Herman JG, Brock MV, Zhou Y, Lu Y, Zhang Z, Yang Y, Guo M. J. Cell. Mol. Med. 18 2499-2511 (2014)
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  18. Ski negatively regulates erythroid differentiation through its interaction with GATA1. Ueki N, Zhang L, Hayman MJ. Mol. Cell. Biol. 24 10118-10125 (2004)
  19. Position dependent responses to discontinuities in the retinal determination network. Salzer CL, Kumar JP. Dev. Biol. 326 121-130 (2009)
  20. How Drosophila change their combs: the Hox gene Sex combs reduced and sex comb variation among Sophophora species. Randsholt NB, Santamaria P. Evol. Dev. 10 121-133 (2008)
  21. Dachshund homologues play a conserved role in islet cell development. Kalousova A, Mavropoulos A, Adams BA, Nekrep N, Li Z, Krauss S, Stainier DY, German MS. Dev. Biol. 348 143-152 (2010)
  22. Structural and functional characterization of a cell cycle associated HDAC1/2 complex reveals the structural basis for complex assembly and nucleosome targeting. Itoh T, Fairall L, Muskett FW, Milano CP, Watson PJ, Arnaudo N, Saleh A, Millard CJ, El-Mezgueldi M, Martino F, Schwabe JW. Nucleic Acids Res. 43 2033-2044 (2015)
  23. The dachshund gene is required for the proper guidance and branching of mushroom body axons in Drosophila melanogaster. Martini SR, Davis RL. J. Neurobiol. 64 133-144 (2005)
  24. Retinal determination genes function along with cell-cell signals to regulate Drosophila eye development: examples of multi-layered regulation by master regulators. Baker NE, Firth LC. Bioessays 33 538-546 (2011)
  25. A conserved transcriptional network regulates lamina development in the Drosophila visual system. Piñeiro C, Lopes CS, Casares F. Development 141 2838-2847 (2014)
  26. The SWI/SNF Subunit INI1 Contains an N-Terminal Winged Helix DNA Binding Domain that Is a Target for Mutations in Schwannomatosis. Allen MD, Freund SM, Zinzalla G, Bycroft M. Structure 23 1344-1349 (2015)
  27. dachshund Potentiates Hedgehog Signaling during Drosophila Retinogenesis. Brás-Pereira C, Potier D, Jacobs J, Aerts S, Casares F, Janody F. PLoS Genet. 12 e1006204 (2016)
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  29. Exome sequencing identifies mutations in ABCD1 and DACH2 in two brothers with a distinct phenotype. Zhang Y, Liu Y, Li Y, Duan Y, Zhang K, Wang J, Dai Y. BMC Med. Genet. 15 105 (2014)
  30. Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease. Tecalco-Cruz AC, Ríos-López DG, Vázquez-Victorio G, Rosales-Alvarez RE, Macías-Silva M. Signal Transduct Target Ther 3 15 (2018)
  31. First Insights into the Subterranean Crustacean Bathynellacea Transcriptome: Transcriptionally Reduced Opsin Repertoire and Evidence of Conserved Homeostasis Regulatory Mechanisms. Kim BM, Kang S, Ahn DH, Kim JH, Ahn I, Lee CW, Cho JL, Min GS, Park H. PLoS ONE 12 e0170424 (2017)