Review on DKK1 (dickkopf homolog 1 (Xenopus laevis)), with data on DNA, on the protein encoded, and where the gene is implicated

Aguilera, Oscar

Munoz, Alberto

Atlas of Genetics and Cytogenetics in Oncology and Haematology

I-Revues

  
 
 
 
 
Gene Section 
Mini Review 
 
Atlas Genet Cytogenet Oncol Haematol. 2007;11(4)  266 
Atlas of Genetics and Cytogenetics 
in Oncology and Haematology                         
                         OPEN ACCESS JOURNAL AT INIST-CNRS 
DKK1 (dickkopf homolog 1 (Xenopus laevis)) 
Oscar Aguilera, Alberto Munoz 
Instituto de Investigaciones Biomedicas 'Alberto Sols', C/ Arturo Duperier n4, Madrid, Spain 
Published in Atlas Database: April 2007 
Online updated version: http://AtlasGeneticsOncology.org/Genes/DKK1ID44007ch10q11.html  
DOI: 10.4267/2042/15942 
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence. 
© 2007 Atlas of Genetics and Cytogenetics in Oncology and Haematology 
 
Identity 
Hugo: DKK1 
Other names: Dickkkopf-1; DKK-1; mdkk1; hDkk1; 
dickkopf (Xenopus laevis) homolog 1; SK 
Location: 10q11.2 
DNA/RNA 
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. 
 
 
hDKK1 contains 3 introns and 4 exons (depictured in red). 
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 encodes 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 
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. 
 
DKK1 (dickkopf homolog 1 (Xenopus laevis)) Aguilera O, Munoz A 
 
 
 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2007;11(4)  267 
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. 
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. 
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. 
References 
Glinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, 
Niehrs C. Dickkopf-1 is a member of a new family of secreted 
proteins and functions in head induction. Nature 1998;391:357-
362. 
Bafico A, Liu G, Yaniv A, Gazit A, Aaronson SA. Novel 
mechanism of Wnt signalling inhibition mediated by Dickkopf-1 
interaction with LRP6/Arrow. Nat Cell Biol 2001;3:683-686. 
 
Semënov MV, Tamai K, Brott BK, Kühl M, Sokol S, He X. Head 
inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr 
Biol 2001;11:951-961. 
Grotewold L, Rüther U. The Wnt antagonist Dickkopf-1 is 
regulated by Bmp signaling and c-Jun and modulates 
programmed cell death. EMBO J 2002;21:966-975. 
Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, 
Shaughnessy JD Jr. The role of the Wnt-signaling antagonist 
DKK1 in the development of osteolytic lesions in multiple 
myeloma. N Engl J Med 2003;349:2483-2494. 
Caricasole A, Copani A, Caraci F, Aronica E, Rozemuller AJ, 
Caruso A, Storto M, Gaviraghi G, Terstappen GC, Nicoletti F. 
Induction of Dickkopf-1, a negative modulator of the Wnt 
pathway, is associated with neuronal degeneration in 
Alzheimer's brain. J Neurosci 2004;24:6021-6027. 
Mikheev AM, Mikheeva SA, Liu B, Cohen P, Zarbl H. A 
functional genomics approach for the identification of putative 
tumor suppressor genes: Dickkopf-1 as suppressor of HeLa 
cell transformation. Carcinogenesis 2004;25:47-59. 
Chamorro MN, Schwartz DR, Vonica A, Brivanlou AH, Cho KR, 
Varmus HE. FGF-20 and DKK1 are transcriptional targets of 
beta-catenin and FGF-20 is implicated in cancer and 
development. EMBO J 2005;24:73-84. 
González-Sancho JM, Aguilera O, García JM, Pendás-Franco 
N, Peña C, Cal S, García de Herreros A, Bonilla F, Muñoz A. 
The Wnt antagonist DICKKOPF-1 gene is a downstream target 
of beta-catenin/TCF and is downregulated in human colon 
cancer. Oncogene 2005;24:1098-1103. 
Aguilera O, Fraga MF, Ballestar E, Paz MF, Herranz M, 
Espada J, García JM, Muñoz A, Esteller M, González-Sancho 
JM. Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 
(DKK-1) gene in human colorectal cancer. Oncogene 
2006;25:4116-4121. 
Politou MC, Heath DJ, Rahemtulla A, Szydlo R, 
Anagnostopoulos A, Dimopoulos MA, Croucher PI, Terpos E. 
Serum concentrations of Dickkopf-1 protein are increased in 
patients with multiple myeloma and reduced after autologous 
stem cell transplantation. Int J Cancer 2006;119:1728-1731. 
Aguilera O, Peña  C, García JM, Larriba MJ, Ordóñez-Morán 
P, Navarro D, Barbáchano A, de Silanes IL, Ballestar E, Fraga 
MF, Esteller M, Gamallo C, Bonilla F, González-Sancho JM, 
Muñoz A. The Wnt antagonist DICKKOPF-1 gene is induced 
by 1(alpha),25-dihydroxyvitamin D3 associated to the 
differentiation of human colon cancer cells. Carcinogenesis 
2007;[Epub ahead of print]. 
Busceti CL, Biagioni F, Aronica E, Riozzi B, Storto M, Battaglia 
G, Giorgi FS, Gradini R, Fornai F, Caricasole A, Nicoletti F, 
Bruno V. Induction of the wnt inhibitor, dickkopf-1, is 
associated with neurodegeneration related to temporal lobe 
epilepsy. Epilepsia 2007;48:694-705. 
This article should be referenced as such: 
Aguilera O, Munoz A. DKK1 (dickkopf homolog 1 (Xenopus 
laevis)). Atlas Genet Cytogenet Oncol Haematol.2007; 
11(4):266-267. 
 
 
 


DKK1 (dickkopf homolog 1 (Xenopus laevis))

Abstract

Similar works

Full text

Available Versions

I-Revues