DKK1

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Dickkopf WNT signaling pathway inhibitor 1
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols DKK1 ; DKK-1; SK
External IDs OMIM605189 MGI1329040 HomoloGene7689 ChEMBL: 6024 GeneCards: DKK1 Gene
RNA expression pattern
PBB GE DKK1 204602 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 22943 13380
Ensembl ENSG00000107984 ENSMUSG00000024868
UniProt O94907 O54908
RefSeq (mRNA) NM_012242 NM_010051
RefSeq (protein) NP_036374 NP_034181
Location (UCSC) Chr 10:
54.07 – 54.08 Mb
Chr 19:
30.55 – 30.55 Mb
PubMed search [1] [2]

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

Function[edit]

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] The dickkopf protein encoded by DKK1 is an antagonistic inhibitor of the WNT signaling pathway that acts by isolating the LRP6 co-receptor so that it cannot aid in activating the WNT signaling pathway.[3] This inhibition plays a key role in head and forelimb development during anterior morphogenesis of the embryo.[1]

Interactions[edit]

DKK1 has been shown to interact with LRP6.[4]

Clinical significance[edit]

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[edit]

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.[2] This evidence supports the idea that inhibition of the Wnt signaling pathway by DKK1 is crucial to proper cranial development.

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 body against DKK-1 reversed DHT effects on outer root sheath keratinocytes.[5] DKK-1 expression is attenuated by L-threonate in vitro, with the latter a metabolite of ascorbate.[6]

References[edit]

  1. ^ a b c "Entrez Gene: DKK1 dickkopf homolog 1 (Xenopus laevis)". 
  2. ^ a b Mukhopadhyay M, Shtrom S, Rodriguez-Esteban C, Chen L, Tsukui T, Gomer L et al. (Sep 2001). "Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse". Developmental Cell 1 (3). PMID 11702953. 
  3. ^ Lewis SL, Khoo PL, De Young RA, Steiner K, Wilcock C, Mukhopadhyay M et al. (May 2008). "Dkk1 and Wnt3 interact to control head morphogenesis in the mouse". Development 135 (10). doi:10.1242/dev.018853. PMID 18403408. 
  4. ^ 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. 
  5. ^ Kwack MH, Sung YK, Chung EJ, Im SU, Ahn JS, Kim MK et al. (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. 
  6. ^ 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[edit]