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DACH1  -  dachshund family transcription factor 1

Homo sapiens

Synonyms: DACH, Dach1, Dachshund homolog 1
 
 
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Disease relevance of DACH1

  • Herein, DACH1 was found to be expressed in breast cancer cell lines and to inhibit transforming growth factor-beta (TGF-beta)-induced apoptosis [1].
  • The microarray data for DACH1 and EVI1 were validated using quantitative real-time PCR on 22 microdissected ovarian cancer specimens [2].
  • A panel of human cell lines was studied and most notably a large proportion of neuroblastomas expressed DACH mRNA [3].
  • A Phase 2 trial of the liposomal DACH platinum L-NDDP in patients with therapy-refractory advanced colorectal cancer [4].
  • Our results suggest that defective protein-protein interactions of the mutations in the EYA domain underlie BOR syndrome and that SIX, DACH, and/or G proteins are possibly involved in the pathogenic processes [5].
 

High impact information on DACH1

  • The cell fate determination factor, DACH1, arrests breast tumor proliferation and growth in vivo providing a new mechanistic and potential therapeutic insight into this common disease [6].
  • Here, DACH1 inhibited oncogene-mediated breast oncogenesis, blocking breast cancer epithelial cell DNA synthesis, colony formation, growth in Matrigel, and tumor growth in mice [6].
  • Although EYA proteins interact with members of the SIX and DACH protein families in a conserved network that regulates early embryonic development, this finding shows that EYA4 is also important post-developmentally for continued function of the mature organ of Corti [7].
  • In general, cross-resistance to mixed amine analogues was partial in cisplatin- and tetraplatin-resistant cells and decreased (in L1210/DDP and 2780CP) or increased (in L1210/DACH and 2780TP) with increase in the alicyclic ring size [8].
  • DACH1 inhibits transforming growth factor-beta signaling through binding Smad4 [1].
 

Chemical compound and disease context of DACH1

 

Biological context of DACH1

 

Anatomical context of DACH1

  • The mouse DACH1 protein was immunolocalized to specific cell types within the developing kidneys, eyes, cochleae, and limb buds [10].
  • Dach mRNA expression in the mouse E11.5 embryo was observed primarily in the fore and hind limbs, as well as in the somites [3].
  • RNase protection analysis showed the highest Dach mRNA expression in the adult mouse kidney and lung, whereas lower expression was detected in the brain and testis [3].
  • The bis(platinum) compounds showed greater activity in vitro against murine tumor cell lines resistant to either cisplatin or DACH ([Pt(DACH)Cl2]) [11].
  • Cisplatin and tetraplatin(IV) produced strong damage and DACH RR(II) and cis-[Pt(II)Cl,2(iPrNH2)2] weak DNA damage in intact HeLa cells [12].
 

Associations of DACH1 with chemical compounds

  • The formation of the prognosed complexes [Pt(DACH)(L-Met-S,N)]+ and [Pt(DACH)(5'-GMP)2]2- (DACH = 1,2-diaminocyclohexane) could be proved directly by using CE-ESI-MS [13].
  • All these interactions are shown to apply also when diA = dach (1,2-diaminocyclohexane), even though this chiral primary diamine has only small N-H atoms on each side of the coordination plane [14].
  • The new results show that at acidic and neutral pH the induction of asymmetry from the dach ligand to the HT rotamers is governed by the G-to-G dipole-dipole interaction, which is greater for the six-membered ring of each guanine leaning towards the cis-G [14].
  • Protein binding is selective for DNA modified with cisplatin, [Pt(en)Cl2] (en, ethylenediamine), and [Pt(dach)Cl2] (dach, 1,2-diaminocyclohexane) but not with chemotherapeutically inactive trans-diamminedichloroplatinum(II) or monofunctionally coordinating [Pt(dien)Cl]Cl (dien, diethylenetriamine) complexes [15].
  • The dach complex c,t-2a, reacts with ampy, 2,2'-bipyridine (bipy), and 1,10-phenanthroline (phen) in refluxing THF to form the substituted cis-dihydride complexes c,t-2b, (OC-6-13)-RuH2(PPh3)2(bipy) (c,t-2c with trans PPh3 groups) and (OC-6-13)-RuH2(PPh3)2(phen), c,t-2d, respectively [16].
 

Other interactions of DACH1

 

Analytical, diagnostic and therapeutic context of DACH1

  • RT/PCR analysis readily detected Dach mRNA in the adult mouse cornea and retina [3].

References

  1. DACH1 inhibits transforming growth factor-beta signaling through binding Smad4. Wu, K., Yang, Y., Wang, C., Davoli, M.A., D'Amico, M., Li, A., Cveklova, K., Kozmik, Z., Lisanti, M.P., Russell, R.G., Cvekl, A., Pestell, R.G. J. Biol. Chem. (2003) [Pubmed]
  2. Expression Profiling Identifies Altered Expression of Genes That Contribute to the Inhibition of Transforming Growth Factor-{beta} Signaling in Ovarian Cancer. Sunde, J.S., Donninger, H., Wu, K., Johnson, M.E., Pestell, R.G., Rose, G.S., Mok, S.C., Brady, J., Bonome, T., Birrer, M.J. Cancer Res. (2006) [Pubmed]
  3. Molecular cloning and expression of the human and mouse homologues of the Drosophila dachshund gene. Kozmik, Z., Pfeffer, P., Kralova, J., Paces, J., Paces, V., Kalousova, A., Cvekl, A. Dev. Genes Evol. (1999) [Pubmed]
  4. A Phase 2 trial of the liposomal DACH platinum L-NDDP in patients with therapy-refractory advanced colorectal cancer. Dragovich, T., Mendelson, D., Kurtin, S., Richardson, K., Von Hoff, D., Hoos, A. Cancer Chemother. Pharmacol. (2006) [Pubmed]
  5. Impaired interactions between mouse Eyal harboring mutations found in patients with branchio-oto-renal syndrome and Six, Dach, and G proteins. Ozaki, H., Watanabe, Y., Ikeda, K., Kawakami, K. J. Hum. Genet. (2002) [Pubmed]
  6. 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, M.P., Sauter, G., Russell, R.G., Cvekl, A., Pestell, R.G. Mol. Cell. Biol. (2006) [Pubmed]
  7. Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus. Wayne, S., Robertson, N.G., DeClau, F., Chen, N., Verhoeven, K., Prasad, S., Tranebjärg, L., Morton, C.C., Ryan, A.F., Van Camp, G., Smith, R.J. Hum. Mol. Genet. (2001) [Pubmed]
  8. Biochemical pharmacology of homologous alicyclic mixed amine platinum(II) complexes in sensitive and resistant tumor cell lines. Yoshida, M., Khokhar, A.R., Siddik, Z.H. Cancer Res. (1994) [Pubmed]
  9. Localization of the human homologue of the Drosophila dachshund gene (DACH) to chromosome 13q21. Kozmik, Z., Cvekl, A. Genomics (1999) [Pubmed]
  10. DACH: genomic characterization, evaluation as a candidate for postaxial polydactyly type A2, and developmental expression pattern of the mouse homologue. Ayres, J.A., Shum, L., Akarsu, A.N., Dashner, R., Takahashi, K., Ikura, T., Slavkin, H.C., Nuckolls, G.H. Genomics (2001) [Pubmed]
  11. Anticancer activity in murine and human tumor cell lines of bis(platinum) complexes incorporating straight-chain aliphatic diamine linker groups. Kraker, A.J., Hoeschele, J.D., Elliott, W.L., Showalter, H.D., Sercel, A.D., Farrell, N.P. J. Med. Chem. (1992) [Pubmed]
  12. DNA sequence selectivity of cisplatin analogues in intact human cells. Murray, V., Whittaker, J., McFadyen, W.D. Chem. Biol. Interact. (1998) [Pubmed]
  13. Application of capillary electrophoresis-mass spectrometry for the investigation of the binding behavior of oxaliplatin to 5'-GMP in the presence of the sulfur-containing amino acid L-methionine. Strickmann, D.B., Kong, A., Keppler, B.K. Electrophoresis (2002) [Pubmed]
  14. Rotamer stability in cis-[Pt(diA)G2] complexes (diA = diamine derivative and G = guanine derivative) mediated by carrier-ligand amine stereochemistry as revealed by circular dichroism spectroscopy. Benedetti, M., Marzilli, L.G., Natile, G. Chemistry (Weinheim an der Bergstrasse, Germany) (2005) [Pubmed]
  15. Characterization of a DNA damage-recognition protein from mammalian cells that binds specifically to intrastrand d(GpG) and d(ApG) DNA adducts of the anticancer drug cisplatin. Donahue, B.A., Augot, M., Bellon, S.F., Treiber, D.K., Toney, J.H., Lippard, S.J., Essigmann, J.M. Biochemistry (1990) [Pubmed]
  16. Chemistry of ruthenium(II) monohydride and dihydride complexes containing pyridyl donor ligands including catalytic ketone H2-hydrogenation. Abdur-Rashid, K., Abbel, R., Hadzovic, A., Lough, A.J., Morris, R.H. Inorganic chemistry. (2005) [Pubmed]
 
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