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DKK1 (dickkopf homolog 1 (Xenopus laevis))

Written2007-04Oscar Aguilera, Alberto Munoz
Instituto de Investigaciones Biomedicas Alberto Sols, C/ Arturo Duperier n4, Madrid (Spain); oaguilera@iib.uam.es .

(Note : for Links provided by Atlas : click)

Identity

Other aliasDickkkopf-1
DKK-1
mdkk1
hDkk1
dickkopf (Xenopus laevis) homolog 1
SK
LocusID (NCBI) 22943
Atlas_Id 44007
Location 10q21.1  [Link to chromosome band 10q21]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
SRI (7q21.12) / DKK1 (10q21.1)

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

Note
  
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.
  

Bibliography

The Wnt antagonist DICKKOPF-1 gene is induced by 1alpha,25-dihydroxyvitamin D3 associated to the differentiation of human colon cancer cells.
Aguilera O, Peña C, García JM, Larriba MJ, Ordóñez-Morán P, Navarro D, Barb´chano A, López de Silanes I, Ballestar E, Fraga MF, Esteller M, Gamallo C, Bonilla F, Gonz´lez-Sancho JM, Muñoz A
Carcinogenesis. 2007 ; 28 (9) : 1877-1884.
PMID 17449905
 
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
 
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
 
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
 
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
 
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
 
The Wnt antagonist DICKKOPF-1 gene is a downstream target of beta-catenin/TCF and is downregulated in human colon cancer.
Gonz´lez-Sancho JM, Aguilera O, García JM, Pend´s-Franco N, Peña C, Cal S, García de Herreros A, Bonilla F, Muñoz A
Oncogene. 2005 ; 24 (6) : 1098-1103.
PMID 15592505
 
The Wnt antagonist Dickkopf-1 is regulated by Bmp signaling and c-Jun and modulates programmed cell death.
Grotewold L, Rüther U
The EMBO journal. 2002 ; 21 (5) : 966-975.
PMID 11867524
 
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
 
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
 
Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6.
Semënov MV, Tamai K, Brott BK, Kühl M, Sokol S, He X
Current biology : CB. 2001 ; 11 (12) : 951-961.
PMID 11448771
 
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
 

Citation

This paper should be referenced as such :
Aguilera, Oscar ; Munoz, Alberto
DKK1 (dickkopf homolog 1 (Xenopus laevis))
Atlas Genet Cytogenet Oncol Haematol. 2007;11(4):266-267.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/DKK1ID44007ch10q11.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  Multiple Myeloma


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Colon: Colorectal adenocarcinoma


External links

Nomenclature
Cards
AtlasDKK1ID44007ch10q11.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)22943
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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indexed on : Thu Oct 18 17:33:54 CEST 2018

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