DKK1: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Robot: Automated text replacement (-{{WikiDoc Cardiology Network Infobox}} +, -<references /> +{{reflist|2}}, -{{reflist}} +{{reflist|2}}))
 
 
(One intermediate revision by one other user not shown)
Line 1: Line 1:
<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Dickkopf-related protein 1''' is a [[protein]] that in humans is encoded by the ''DKK1'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: DKK1 dickkopf homolog 1 (Xenopus laevis)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=22943| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Dickkopf homolog 1 (Xenopus laevis)
| HGNCid = 2891
| Symbol = DKK1
| AltSymbols =; DKK-1; SK
| OMIM = 605189
| ECnumber = 
| Homologene = 7689
| MGIid = 1329040
| GeneAtlas_image1 = PBB_GE_DKK1_204602_at_tn.png
| Function = {{GNF_GO|id=GO:0004871 |text = signal transducer activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0008083 |text = growth factor activity}} {{GNF_GO|id=GO:0050750 |text = low-density lipoprotein receptor binding}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005886 |text = plasma membrane}}
| Process = {{GNF_GO|id=GO:0007275 |text = multicellular organismal development}} {{GNF_GO|id=GO:0016055 |text = Wnt receptor signaling pathway}} {{GNF_GO|id=GO:0030178 |text = negative regulation of Wnt receptor signaling pathway}} {{GNF_GO|id=GO:0030326 |text = embryonic limb morphogenesis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 22943
    | Hs_Ensembl = ENSG00000107984
    | Hs_RefseqProtein = NP_036374
    | Hs_RefseqmRNA = NM_012242
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 10
    | Hs_GenLoc_start = 53744064
    | Hs_GenLoc_end = 53747595
    | Hs_Uniprot = O94907
    | Mm_EntrezGene = 13380
    | Mm_Ensembl = ENSMUSG00000024868
    | Mm_RefseqmRNA = NM_010051
    | Mm_RefseqProtein = NP_034181
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 19
    | Mm_GenLoc_start = 30611873
    | Mm_GenLoc_end = 30615493
    | Mm_Uniprot = Q80UL5
  }}
}}
'''Dickkopf homolog 1 (Xenopus laevis)''', also known as '''DKK1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: DKK1 dickkopf homolog 1 (Xenopus laevis)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=22943| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
This gene encodes a protein that is a member of the [[dickkopf]] family. It is a secreted protein with two [[cysteine]] rich regions and is involved in embryonic development through its inhibition of the [[Wnt signaling pathway]].  Dickkopf WNT signaling pathway inhibitor 1 (Dkk1) is a protein-coding gene that acts from the anterior visceral [[endoderm]].<ref>{{cite journal | vauthors = Schneider VA, Mercola M | year = 1999 | title = Spatially distinct head and heart inducers within the Xenopus organizer region | url = | journal = Curr Biol | volume = 9 | issue = | pages = 800–809 | doi=10.1016/s0960-9822(99)80363-7}}</ref><ref name = "Mukhopadhyay_2001">{{cite journal | vauthors = Mukhopadhyay M, Shtrom S, Rodriguez-Esteban C, Chen L, Tsukui T, Gomer L, Dorward DW, Glinka A, Grinberg A, Huang SP, Niehrs C, Izpisúa Belmonte JC, Westphal H | title = Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse | journal = Developmental Cell | volume = 1 | issue = 3 | date = Sep 2001 | pmid = 11702953 | pages=423–34 | doi=10.1016/s1534-5807(01)00041-7}}</ref>  The dickkopf protein encoded by DKK1 is an antagonist of the Wnt/β-catenin signalling pathway that acts by isolating the [[LRP6]] co-receptor so that it cannot aid in activating the WNT signaling pathway.<ref name = "Lewis_2008" >{{cite journal | vauthors = Lewis SL, Khoo PL, De Young RA, Steiner K, Wilcock C, Mukhopadhyay M, Westphal H, Jamieson RV, Robb L, Tam PP | title = Dkk1 and Wnt3 interact to control head morphogenesis in the mouse | journal = Development | volume = 135 | issue = 10 | date = May 2008 | pmid = 18403408 | doi = 10.1242/dev.018853 | pages=1791–801}}</ref> DKK1 was also demonstrated to antagonize the Wnt/β-catenin pathway via a reduction in β-catenin and an increase in OCT4 expression.<ref name = "Ou">{{cite journal | vauthors = Ou L, Fang L, Tang H, Qiao H, Zhang X, Wang Z | title = Dickkopf Wnt signaling pathway inhibitor 1 regulates the differentiation of mouse embryonic stem cells in vitro and in vivo | journal = Molecular Medicine Reports | volume = 13 | issue = 1 | pages = 720–30 | date = Jan 2016 | pmid = 26648540 | pmc = 4686056 | doi = 10.3892/mmr.2015.4586 }}</ref>
{{PBB_Summary
This inhibition plays a key role in heart, head and forelimb development during anterior [[morphogenesis]] of the embryo.<ref name="entrez" /><ref>{{cite journal | vauthors = Schneider VA, Mercola M | year = 2001 | title = Wnt antagonism initiates cardiogenesis in Xenopus laevis | journal = Genes Dev | volume = 15 | issue = | pages = 304–315 | doi=10.1101/gad.855601 | pmid=11159911 | pmc=312618}}</ref>
| section_title =
| summary_text = This gene encodes a protein that is a member of the dickkopf family. It is a secreted protein with two cysteine rich regions and is involved in embryonic development through its inhibition of the WNT signaling pathway. Elevated levels of DKK1 in bone marrow plasma and peripheral blood is associated with the presence of osteolytic bone lesions in patients with multiple myeloma.<ref name="entrez">{{cite web | title = Entrez Gene: DKK1 dickkopf homolog 1 (Xenopus laevis)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=22943| accessdate = }}</ref>
}}


==References==
== Interactions ==
{{reflist|2}}
 
==Further reading==
DKK1 has been shown to [[Protein-protein interaction|interact]] with [[LRP6]]<ref name="pmid11448771">{{cite journal | vauthors = Semënov MV, Tamai K, Brott BK, Kühl M, Sokol S, He X | title = Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6 | journal = Current Biology | volume = 11 | issue = 12 | pages = 951–61 | date = Jun 2001 | pmid = 11448771 | doi = 10.1016/S0960-9822(01)00290-1 }}</ref> and is a high affinity ligand of [[KREMEN1|Kremen proteins]].<ref name="Nakamura_2008">{{cite journal | vauthors = Nakamura T, Nakamura T, Matsumoto K | title = The functions and possible significance of Kremen as the gatekeeper of Wnt signalling in development and pathology | journal = Journal of Cellular and Molecular Medicine | volume = 12 | issue = 2 | pages = 391–408 | year = 2008 | pmid = 18088386 | pmc = 3822531 | doi = 10.1111/j.1582-4934.2007.00201.x }}</ref>
{{refbegin | 2}}
 
{{PBB_Further_reading
== Clinical significance ==
| citations =  
 
*{{cite journal | author=Fedi P, Bafico A, Nieto Soria A, ''et al.'' |title=Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling. |journal=J. Biol. Chem. |volume=274 |issue= 27 |pages= 19465-72 |year= 1999 |pmid= 10383463 |doi= }}
Elevated levels of DKK1 in bone marrow, plasma and peripheral blood is associated with the presence of [[osteolytic bone lesions]] in patients with [[multiple myeloma]].<ref name="entrez" />
*{{cite journal  | author=Krupnik VE, Sharp JD, Jiang C, ''et al.'' |title=Functional and structural diversity of the human Dickkopf gene family. |journal=Gene |volume=238 |issue= 2 |pages= 301-13 |year= 1999 |pmid= 10570958 |doi= }}
 
*{{cite journal | author=Roessler E, Du Y, Glinka A, ''et al.'' |title=The genomic structure, chromosome location, and analysis of the human DKK1 head inducer gene as a candidate for holoprosencephaly. |journal=Cytogenet. Cell Genet. |volume=89 |issue= 3-4 |pages= 220-4 |year= 2000 |pmid= 10965128 |doi= }}
== Animal studies ==
*{{cite journal | author=Mao B, Wu W, Li Y, ''et al.'' |title=LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. |journal=Nature |volume=411 |issue= 6835 |pages= 321-5 |year= 2001 |pmid= 11357136 |doi= 10.1038/35077108 }}
 
*{{cite journal | author=Semënov MV, Tamai K, Brott BK, ''et al.'' |title=Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. |journal=Curr. Biol. |volume=11 |issue= 12 |pages= 951-61 |year= 2001 |pmid= 11448771 |doi= }}
Scientists have created a DKK1 knockout model in mice that revealed the effects of this gene. All mice that were homozygous for the DKK1 knockout were dead at birth due to defects in the cranium and structures formed by the neural crest, such as failed development of eyes, olfactory placodes, frontonasal mass and mandibular processes, as well as incomplete development of the forebrain and midbrain and fusion of the digits of the forelimb.<ref name = "Mukhopadhyay_2001"/> This evidence supports the idea that inhibition of the Wnt signaling pathway by DKK1 is crucial to proper cranial development.
*{{cite journal  | author=Zorn AM |title=Wnt signalling: antagonistic Dickkopfs. |journal=Curr. Biol. |volume=11 |issue= 15 |pages= R592-5 |year= 2001 |pmid= 11516963 |doi=  }}
 
*{{cite journal | author=Shou J, Ali-Osman F, Multani AS, ''et al.'' |title=Human Dkk-1, a gene encoding a Wnt antagonist, responds to DNA damage and its overexpression sensitizes brain tumor cells to apoptosis following alkylation damage of DNA. |journal=Oncogene |volume=21 |issue= 6 |pages= 878-89 |year= 2002 |pmid= 11840333 |doi= 10.1038/sj.onc.1205138 }}
==In vitro studies==
*{{cite journal | author=Mao B, Wu W, Davidson G, ''et al.'' |title=Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. |journal=Nature |volume=417 |issue= 6889 |pages= 664-7 |year= 2002 |pmid= 12050670 |doi= 10.1038/nature756 }}
 
*{{cite journal | author=Brott BK, Sokol SY |title=Regulation of Wnt/LRP signaling by distinct domains of Dickkopf proteins. |journal=Mol. Cell. Biol. |volume=22 |issue= 17 |pages= 6100-10 |year= 2002 |pmid= 12167704 |doi= }}
DKK1 is one of the most upregulated genes in androgen-potentiated balding, with DKK-1 [[messenger RNA]] upregulated a few hours after DHT treatment of hair follicles at the [[dermal papilla]] ''[[in vitro]]''. Neutralizing antibody against DKK-1 reversed DHT effects on outer root sheath keratinocytes.<ref name="pmid17657240">{{cite journal | vauthors = Kwack MH, Sung YK, Chung EJ, Im SU, Ahn JS, Kim MK, Kim JC | title = Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes | journal = The Journal of Investigative Dermatology | volume = 128 | issue = 2 | pages = 262–9 | date = Feb 2008 | pmid = 17657240 | doi = 10.1038/sj.jid.5700999 }}</ref> DKK-1 expression is attenuated by [[L-threonate]] ''in vitro'', with the latter a metabolite of [[ascorbate]].<ref name="pmid21034532">{{cite journal | vauthors = Kwack MH, Ahn JS, Kim MK, Kim JC, Sung YK | title = Preventable effect of L-threonate, an ascorbate metabolite, on androgen-driven balding via repression of dihydrotestosterone-induced dickkopf-1 expression in human hair dermal papilla cells | journal = BMB Reports | volume = 43 | issue = 10 | pages = 688–92 | date = Oct 2010 | pmid = 21034532 | doi = 10.5483/BMBRep.2010.43.10.688 }}</ref>
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
 
*{{cite journal | author=Gregory CA, Singh H, Perry AS, Prockop DJ |title=The Wnt signaling inhibitor dickkopf-1 is required for reentry into the cell cycle of human adult stem cells from bone marrow. |journal=J. Biol. Chem. |volume=278 |issue= 30 |pages= 28067-78 |year= 2003 |pmid= 12740383 |doi= 10.1074/jbc.M300373200 }}
== References ==
*{{cite journal | author=Clark HF, Gurney AL, Abaya E, ''et al.'' |title=The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. |journal=Genome Res. |volume=13 |issue= 10 |pages= 2265-70 |year= 2003 |pmid= 12975309 |doi= 10.1101/gr.1293003 }}
{{reflist|33em}}
*{{cite journal | author=Tian E, Zhan F, Walker R, ''et al.'' |title=The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. |journal=N. Engl. J. Med. |volume=349 |issue= 26 |pages= 2483-94 |year= 2004 |pmid= 14695408 |doi= 10.1056/NEJMoa030847 }}
 
*{{cite journal | author=Yamaguchi Y, Itami S, Watabe H, ''et al.'' |title=Mesenchymal-epithelial interactions in the skin: increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation. |journal=J. Cell Biol. |volume=165 |issue= 2 |pages= 275-85 |year= 2004 |pmid= 15117970 |doi= 10.1083/jcb.200311122 }}
== Further reading ==
*{{cite journal | author=Caricasole A, Copani A, Caraci F, ''et al.'' |title=Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer's brain. |journal=J. Neurosci. |volume=24 |issue= 26 |pages= 6021-7 |year= 2004 |pmid= 15229249 |doi= 10.1523/JNEUROSCI.1381-04.2004 }}
{{refbegin|33em}}
*{{cite journal | author=Colland F, Jacq X, Trouplin V, ''et al.'' |title=Functional proteomics mapping of a human signaling pathway. |journal=Genome Res. |volume=14 |issue= 7 |pages= 1324-32 |year= 2004 |pmid= 15231748 |doi= 10.1101/gr.2334104 }}
* {{cite journal | vauthors = Fedi P, Bafico A, Nieto Soria A, Burgess WH, Miki T, Bottaro DP, Kraus MH, Aaronson SA | title = Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling | journal = The Journal of Biological Chemistry | volume = 274 | issue = 27 | pages = 19465–72 | date = Jul 1999 | pmid = 10383463 | doi = 10.1074/jbc.274.27.19465 }}
*{{cite journal | author=Zhang Z, Henzel WJ |title=Signal peptide prediction based on analysis of experimentally verified cleavage sites. |journal=Protein Sci. |volume=13 |issue= 10 |pages= 2819-24 |year= 2005 |pmid= 15340161 |doi= 10.1110/ps.04682504 }}
* {{cite journal | vauthors = Krupnik VE, Sharp JD, Jiang C, Robison K, Chickering TW, Amaravadi L, Brown DE, Guyot D, Mays G, Leiby K, Chang B, Duong T, Goodearl AD, Gearing DP, Sokol SY, McCarthy SA | title = Functional and structural diversity of the human Dickkopf gene family | journal = Gene | volume = 238 | issue = 2 | pages = 301–13 | date = Oct 1999 | pmid = 10570958 | doi = 10.1016/S0378-1119(99)00365-0 }}
*{{cite journal | author=Niida A, Hiroko T, Kasai M, ''et al.'' |title=DKK1, a negative regulator of Wnt signaling, is a target of the beta-catenin/TCF pathway. |journal=Oncogene |volume=23 |issue= 52 |pages= 8520-6 |year= 2004 |pmid= 15378020 |doi= 10.1038/sj.onc.1207892 }}
* {{cite journal | vauthors = Roessler E, Du Y, Glinka A, Dutra A, Niehrs C, Muenke M | title = The genomic structure, chromosome location, and analysis of the human DKK1 head inducer gene as a candidate for holoprosencephaly | journal = Cytogenetics and Cell Genetics | volume = 89 | issue = 3–4 | pages = 220–4 | year = 2000 | pmid = 10965128 | doi = 10.1159/000015618 }}
*{{cite journal | author=Lee AY, He B, You L, ''et al.'' |title=Dickkopf-1 antagonizes Wnt signaling independent of beta-catenin in human mesothelioma. |journal=Biochem. Biophys. Res. Commun. |volume=323 |issue= 4 |pages= 1246-50 |year= 2004 |pmid= 15451431 |doi= 10.1016/j.bbrc.2004.09.001 }}
* {{cite journal | vauthors = Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, Niehrs C | title = LDL-receptor-related protein 6 is a receptor for Dickkopf proteins | journal = Nature | volume = 411 | issue = 6835 | pages = 321–5 | date = May 2001 | pmid = 11357136 | doi = 10.1038/35077108 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
* {{cite journal | vauthors = Semënov MV, Tamai K, Brott BK, Kühl M, Sokol S, He X | title = Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6 | journal = Current Biology | volume = 11 | issue = 12 | pages = 951–61 | date = Jun 2001 | pmid = 11448771 | doi = 10.1016/S0960-9822(01)00290-1 }}
}}
* {{cite journal | vauthors = Zorn AM | title = Wnt signalling: antagonistic Dickkopfs | journal = Current Biology | volume = 11 | issue = 15 | pages = R592–5 | date = Aug 2001 | pmid = 11516963 | doi = 10.1016/S0960-9822(01)00360-8 }}
* {{cite journal | vauthors = Shou J, Ali-Osman F, Multani AS, Pathak S, Fedi P, Srivenugopal KS | title = Human Dkk-1, a gene encoding a Wnt antagonist, responds to DNA damage and its overexpression sensitizes brain tumor cells to apoptosis following alkylation damage of DNA | journal = Oncogene | volume = 21 | issue = 6 | pages = 878–89 | date = Jan 2002 | pmid = 11840333 | doi = 10.1038/sj.onc.1205138 }}
* {{cite journal | vauthors = Mao B, Wu W, Davidson G, Marhold J, Li M, Mechler BM, Delius H, Hoppe D, Stannek P, Walter C, Glinka A, Niehrs C | title = Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling | journal = Nature | volume = 417 | issue = 6889 | pages = 664–7 | date = Jun 2002 | pmid = 12050670 | doi = 10.1038/nature756 }}
* {{cite journal | vauthors = Aguilera O, Fraga MF, Ballestar E, Paz MF, Herranz M, Espada J, García JM, Muñoz A, Esteller M, González-Sancho JM | title = Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer | journal = Oncogene | volume = 25 | issue = 29 | pages = 4116–21 | date = Jul 2006 | pmid = 16491118 | doi = 10.1038/sj.onc.1209439 }}
* {{cite journal | vauthors = Brott BK, Sokol SY | title = Regulation of Wnt/LRP signaling by distinct domains of Dickkopf proteins | journal = Molecular and Cellular Biology | volume = 22 | issue = 17 | pages = 6100–10 | date = Sep 2002 | pmid = 12167704 | pmc = 133995 | doi = 10.1128/MCB.22.17.6100-6110.2002 }}
* {{cite journal | vauthors = Gregory CA, Singh H, Perry AS, Prockop DJ | title = The Wnt signaling inhibitor dickkopf-1 is required for reentry into the cell cycle of human adult stem cells from bone marrow | journal = The Journal of Biological Chemistry | volume = 278 | issue = 30 | pages = 28067–78 | date = Jul 2003 | pmid = 12740383 | doi = 10.1074/jbc.M300373200 }}
* {{cite journal | vauthors = Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD | title = The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma | journal = The New England Journal of Medicine | volume = 349 | issue = 26 | pages = 2483–94 | date = Dec 2003 | pmid = 14695408 | doi = 10.1056/NEJMoa030847 }}
* {{cite journal | vauthors = Yamaguchi Y, Itami S, Watabe H, Yasumoto K, Abdel-Malek ZA, Kubo T, Rouzaud F, Tanemura A, Yoshikawa K, Hearing VJ | title = Mesenchymal-epithelial interactions in the skin: increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation | journal = The Journal of Cell Biology | volume = 165 | issue = 2 | pages = 275–85 | date = Apr 2004 | pmid = 15117970 | pmc = 2172049 | doi = 10.1083/jcb.200311122 }}
* {{cite journal | vauthors = Caricasole A, Copani A, Caraci F, Aronica E, Rozemuller AJ, Caruso A, Storto M, Gaviraghi G, Terstappen GC, Nicoletti F | title = Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer's brain | journal = The Journal of Neuroscience | volume = 24 | issue = 26 | pages = 6021–7 | date = Jun 2004 | pmid = 15229249 | doi = 10.1523/JNEUROSCI.1381-04.2004 }}
* {{cite journal | vauthors = Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM | title = Functional proteomics mapping of a human signaling pathway | journal = Genome Research | volume = 14 | issue = 7 | pages = 1324–32 | date = Jul 2004 | pmid = 15231748 | pmc = 442148 | doi = 10.1101/gr.2334104 }}
* {{cite journal | vauthors = Zhang Z, Henzel WJ | title = Signal peptide prediction based on analysis of experimentally verified cleavage sites | journal = Protein Science | volume = 13 | issue = 10 | pages = 2819–24 | date = Oct 2004 | pmid = 15340161 | pmc = 2286551 | doi = 10.1110/ps.04682504 }}
* {{cite journal | vauthors = Niida A, Hiroko T, Kasai M, Furukawa Y, Nakamura Y, Suzuki Y, Sugano S, Akiyama T | title = DKK1, a negative regulator of Wnt signaling, is a target of the beta-catenin/TCF pathway | journal = Oncogene | volume = 23 | issue = 52 | pages = 8520–6 | date = Nov 2004 | pmid = 15378020 | doi = 10.1038/sj.onc.1207892 }}
* {{cite journal | vauthors = Lee AY, He B, You L, Xu Z, Mazieres J, Reguart N, Mikami I, Batra S, Jablons DM | title = Dickkopf-1 antagonizes Wnt signaling independent of beta-catenin in human mesothelioma | journal = Biochemical and Biophysical Research Communications | volume = 323 | issue = 4 | pages = 1246–50 | date = Oct 2004 | pmid = 15451431 | doi = 10.1016/j.bbrc.2004.09.001 }}
{{refend}}
{{refend}}
{{protein-stub}}
{{WikiDoc Sources}}

Latest revision as of 19:13, 23 December 2018

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Dickkopf-related protein 1 is a protein that in humans is encoded by the DKK1 gene.[1]

Function

This gene encodes a protein that is a member of the dickkopf family. It is a secreted protein with two cysteine rich regions and is involved in embryonic development through its inhibition of the Wnt signaling pathway. Dickkopf WNT signaling pathway inhibitor 1 (Dkk1) is a protein-coding gene that acts from the anterior visceral endoderm.[2][3] The dickkopf protein encoded by DKK1 is an antagonist of the Wnt/β-catenin signalling pathway that acts by isolating the LRP6 co-receptor so that it cannot aid in activating the WNT signaling pathway.[4] DKK1 was also demonstrated to antagonize the Wnt/β-catenin pathway via a reduction in β-catenin and an increase in OCT4 expression.[5] This inhibition plays a key role in heart, head and forelimb development during anterior morphogenesis of the embryo.[1][6]

Interactions

DKK1 has been shown to interact with LRP6[7] and is a high affinity ligand of Kremen proteins.[8]

Clinical significance

Elevated levels of DKK1 in bone marrow, plasma and peripheral blood is associated with the presence of osteolytic bone lesions in patients with multiple myeloma.[1]

Animal studies

Scientists have created a DKK1 knockout model in mice that revealed the effects of this gene. All mice that were homozygous for the DKK1 knockout were dead at birth due to defects in the cranium and structures formed by the neural crest, such as failed development of eyes, olfactory placodes, frontonasal mass and mandibular processes, as well as incomplete development of the forebrain and midbrain and fusion of the digits of the forelimb.[3] This evidence supports the idea that inhibition of the Wnt signaling pathway by DKK1 is crucial to proper cranial development.

In vitro studies

DKK1 is one of the most upregulated genes in androgen-potentiated balding, with DKK-1 messenger RNA upregulated a few hours after DHT treatment of hair follicles at the dermal papilla in vitro. Neutralizing antibody against DKK-1 reversed DHT effects on outer root sheath keratinocytes.[9] DKK-1 expression is attenuated by L-threonate in vitro, with the latter a metabolite of ascorbate.[10]

References

  1. ↑ 1.0 1.1 1.2 "Entrez Gene: DKK1 dickkopf homolog 1 (Xenopus laevis)".
  2. ↑ Schneider VA, Mercola M (1999). "Spatially distinct head and heart inducers within the Xenopus organizer region". Curr Biol. 9: 800–809. doi:10.1016/s0960-9822(99)80363-7.
  3. ↑ 3.0 3.1 Mukhopadhyay M, Shtrom S, Rodriguez-Esteban C, Chen L, Tsukui T, Gomer L, Dorward DW, Glinka A, Grinberg A, Huang SP, Niehrs C, Izpisúa Belmonte JC, Westphal H (Sep 2001). "Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse". Developmental Cell. 1 (3): 423–34. doi:10.1016/s1534-5807(01)00041-7. PMID 11702953.
  4. ↑ Lewis SL, Khoo PL, De Young RA, Steiner K, Wilcock C, Mukhopadhyay M, Westphal H, Jamieson RV, Robb L, Tam PP (May 2008). "Dkk1 and Wnt3 interact to control head morphogenesis in the mouse". Development. 135 (10): 1791–801. doi:10.1242/dev.018853. PMID 18403408.
  5. ↑ Ou L, Fang L, Tang H, Qiao H, Zhang X, Wang Z (Jan 2016). "Dickkopf Wnt signaling pathway inhibitor 1 regulates the differentiation of mouse embryonic stem cells in vitro and in vivo". Molecular Medicine Reports. 13 (1): 720–30. doi:10.3892/mmr.2015.4586. PMC 4686056. PMID 26648540.
  6. ↑ Schneider VA, Mercola M (2001). "Wnt antagonism initiates cardiogenesis in Xenopus laevis". Genes Dev. 15: 304–315. doi:10.1101/gad.855601. PMC 312618. PMID 11159911.
  7. ↑ Semënov MV, Tamai K, Brott BK, Kühl M, Sokol S, He X (Jun 2001). "Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6". Current Biology. 11 (12): 951–61. doi:10.1016/S0960-9822(01)00290-1. PMID 11448771.
  8. ↑ Nakamura T, Nakamura T, Matsumoto K (2008). "The functions and possible significance of Kremen as the gatekeeper of Wnt signalling in development and pathology". Journal of Cellular and Molecular Medicine. 12 (2): 391–408. doi:10.1111/j.1582-4934.2007.00201.x. PMC 3822531. PMID 18088386.
  9. ↑ Kwack MH, Sung YK, Chung EJ, Im SU, Ahn JS, Kim MK, Kim JC (Feb 2008). "Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes". The Journal of Investigative Dermatology. 128 (2): 262–9. doi:10.1038/sj.jid.5700999. PMID 17657240.
  10. ↑ Kwack MH, Ahn JS, Kim MK, Kim JC, Sung YK (Oct 2010). "Preventable effect of L-threonate, an ascorbate metabolite, on androgen-driven balding via repression of dihydrotestosterone-induced dickkopf-1 expression in human hair dermal papilla cells". BMB Reports. 43 (10): 688–92. doi:10.5483/BMBRep.2010.43.10.688. PMID 21034532.

Further reading

Retrieved from "https://www.wikidoc.org/index.php?title=DKK1&oldid=1527319"