Atlas of Genetics and Cytogenetics in Oncology and Haematology
DKK1 (dickkopf homolog 1 (Xenopus laevis))
| Identity |
| Other names | Dickkkopf-1 |
| DKK-1 | |
| mdkk1 | |
| hDkk1 | |
| dickkopf (Xenopus laevis) homolog 1 | |
| SK | |
| HGNC (Hugo) | DKK1 |
| Location | 10q11.2 |
| Location_base_pair | Starts at 53744047 and ends at 53747423 bp from pter ( according to hg18-Mar_2006) [Mapping] |
| DNA/RNA |
 | |
| hDKK1 contains 3 introns and 4 exons (depictured in red). | |
| Description | Position: 53744064 - 53747595 ; Strand: ( + ). DKK1 is present in the contig NT008583 of Genebank; 4 Exon(s) all coding; DNA size 3.07 Kb. |
| Transcription | 1 detected transcript; open reading frame: 1494 bp. |
| Protein |
 | |
| Boxes in red: 1) Signal peptide (1 to 24 aa) 2) Low complexity region (45 to 57 aa) 3) Dickkopf domain (84 to 140 aa) | |
| Description | This gene encodes a protein that is a member of the dickkopf family. HDKK1 encode for a 266 amino acids (aa) protein. The calculated molecular weight is 28.7 KDa. Isoelectric point: 8.74. It possesses two clusters of ten cysteine residues separated by a linker region. |
| Expression | Highly expressed in thyroid, small intestine, stomach, liver, placenta, pancreas, uterus, abdominal cavity, bladder and skin. Weaker expression has been detected in colon and spleen. It is involved in embryonic development through its inhibition of the WNT signaling pathway. |
| Localisation | Extracellular region; secreted protein. |
| Function | Inhibitor of the Wnt signaling pathway. |
| Implicated in |
| Entity | Myeloma bone disease |
| Disease | Patients with multiple myeloma frequently show painful bone lesions and in a recent analysis an increase in Dkk1 in the serum of those patients was noted, whose levels correlated with lesion occurrence. Bone marrow serum containing an elevated level of Dkk1 inhibited the differentiation of osteoblast precursor cells in vitro. Authors propose that Dkk1 produced by myeloma cells blocks osteoblast differentiation, thereby causing the lytic bone lesions. Supporting this idea, treatment of myeloma patients by autologous stem cell transplantation induces a decrease in Dkk1 levels, which is accompanied with elevation of bone formation markers. This raises again interesting therapeutic approaches for interference with the Lrp5/Lrp6-Dkk1 interaction. |
| Entity | Cancer |
| Disease | Different studies displayed changes of Dkk expression in tumor cell lines or tissues. In colon cancer, DKK-1 is a downstream target gene of beta-catenin, as it is in human ovarian endometrioid adenocarcinomas. DKK-1 is silenced in colon cancer by DNA hypermethylation and this correlates with advanced Dukes' stages of colorectal tumorigenesis. DKK-1 overexpression in colon cancer cells or Hela cells reduces colony formation and tumor growth in xenografts, pointing out to a tumor-suppressor function for DKK-1. |
| Entity | Alzheimer |
| Disease | DKK-1 has been also related to neurodegenerative disease. DKK-1 has been shown to be induced in degenerating neurons from Alzheimer patients as well as in cultured neurons challenged with beta-amyloid peptide. Hence, DKK-1 may promote apoptosis in Alzheimer neurons by enhancing Gsk3-mediated phosphorylation of the Tau protein in beta-amyloid-treated neurons. |
| Entity | Epilepsia |
| Disease | Recently, it has been shown that induction of the wnt inhibitor, dickkopf-1, is associated with neurodegeneration related to temporal lobe epilepsy. Strong DKK-1 expression was found in six bioptic samples and in one autoptic sample from patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis. Furthermore, DKK-1 expression was undetectable or very low in autoptic samples from nonepileptic patients or in bioptic samples from patients with complex partial seizures without neuronal loss and/or reactive gliosis in the hippocampus. |
| External links |
| Bibliography |
| Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. |
| Glinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, Niehrs C |
| Nature. 1998 ; 391 (6665) : 357-362. |
| PMID 9450748 |
| Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow. |
| Bafico A, Liu G, Yaniv A, Gazit A, Aaronson SA |
| Nature cell biology. 2001 ; 3 (7) : 683-686. |
| PMID 11433302 |
| Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. |
| Semˆ´nov MV, Tamai K, Brott BK, Kˆºhl M, Sokol S, He X |
| Current biology : CB. 2001 ; 11 (12) : 951-961. |
| PMID 11448771 |
| The Wnt antagonist Dickkopf-1 is regulated by Bmp signaling and c-Jun and modulates programmed cell death. |
| Grotewold L, Rˆºther U |
| The EMBO journal. 2002 ; 21 (5) : 966-975. |
| PMID 11867524 |
| The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. |
| Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD Jr |
| The New England journal of medicine. 2003 ; 349 (26) : 2483-2494. |
| PMID 14695408 |
| Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer's brain. |
| Caricasole A, Copani A, Caraci F, Aronica E, Rozemuller AJ, Caruso A, Storto M, Gaviraghi G, Terstappen GC, Nicoletti F |
| The Journal of neuroscience : the official journal of the Society for Neuroscience. 2004 ; 24 (26) : 6021-6027. |
| PMID 15229249 |
| A functional genomics approach for the identification of putative tumor suppressor genes: Dickkopf-1 as suppressor of HeLa cell transformation. |
| Mikheev AM, Mikheeva SA, Liu B, Cohen P, Zarbl H |
| Carcinogenesis. 2004 ; 25 (1) : 47-59. |
| PMID 14555616 |
| FGF-20 and DKK1 are transcriptional targets of beta-catenin and FGF-20 is implicated in cancer and development. |
| Chamorro MN, Schwartz DR, Vonica A, Brivanlou AH, Cho KR, Varmus HE |
| The EMBO journal. 2005 ; 24 (1) : 73-84. |
| PMID 15592430 |
| The Wnt antagonist DICKKOPF-1 gene is a downstream target of beta-catenin/TCF and is downregulated in human colon cancer. |
| Gonzˆ°lez-Sancho JM, Aguilera O, Garcˆ‚a JM, Pendˆ°s-Franco N, Peˆ±a C, Cal S, Garcˆ‚a de Herreros A, Bonilla F, Muˆ±oz A |
| Oncogene. 2005 ; 24 (6) : 1098-1103. |
| PMID 15592505 |
| Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer. |
| Aguilera O, Fraga MF, Ballestar E, Paz MF, Herranz M, Espada J, Garcˆ‚a JM, Muˆ±oz A, Esteller M, Gonzˆ°lez-Sancho JM |
| Oncogene. 2006 ; 25 (29) : 4116-4121. |
| PMID 16491118 |
| Serum concentrations of Dickkopf-1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation. |
| Politou MC, Heath DJ, Rahemtulla A, Szydlo R, Anagnostopoulos A, Dimopoulos MA, Croucher PI, Terpos E |
| International journal of cancer. Journal international du cancer. 2006 ; 119 (7) : 1728-1731. |
| PMID 16646053 |
| The Wnt antagonist DICKKOPF-1 gene is induced by 1alpha,25-dihydroxyvitamin D3 associated to the differentiation of human colon cancer cells. |
| Aguilera O, Peˆ±a C, Garcˆ‚a JM, Larriba MJ, Ordˆ„ˆ±ez-Morˆ°n P, Navarro D, Barbˆ°chano A, Lˆ„pez de Silanes I, Ballestar E, Fraga MF, Esteller M, Gamallo C, Bonilla F, Gonzˆ°lez-Sancho JM, Muˆ±oz A |
| Carcinogenesis. 2007 ; 28 (9) : 1877-1884. |
| PMID 17449905 |
| Induction of the Wnt inhibitor, Dickkopf-1, is associated with neurodegeneration related to temporal lobe epilepsy. |
| Busceti CL, Biagioni F, Aronica E, Riozzi B, Storto M, Battaglia G, Giorgi FS, Gradini R, Fornai F, Caricasole A, Nicoletti F, Bruno V |
| Epilepsia. 2007 ; 48 (4) : 694-705. |
| PMID 17437412 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 04-2007 | Oscar Aguilera, Alberto Munoz |
| Instituto de Investigaciones Biomedicas "Alberto Sols", C/ Arturo Duperier n4, Madrid (Spain); oaguilera@iib.uam.es . |
| Citation |
| This paper should be referenced as such : |
| Aguilera O, Munoz A . DKK1 (dickkopf homolog 1 (Xenopus laevis)). Atlas Genet Cytogenet Oncol Haematol. April 2007 . URL : http://AtlasGeneticsOncology.org/Genes/DKK1ID44007ch10q11.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sat Jun 27 16:39:51 CEST 2009 |
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