DKK1

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Protein-coding gene in the species Homo sapiens

title: "DKK1" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Protein-coding gene in the species Homo sapiens" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/DKK1" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

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

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. 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. This inhibition plays a key role in heart, head and forelimb development during anterior morphogenesis of the embryo.

Interactions

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

Clinical significance

Elevated levels of DKK1 in bone marrow, plasma and peripheral blood are associated with the presence of osteolytic bone lesions in patients with multiple myeloma. Due to the role of DKK1 in inflammation induced bone loss DKK1 is under investigation as target for therapeutic strategies in medicine and dentistry.

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. 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. DKK-1 expression is attenuated by L-threonate in vitro, with the latter a metabolite of ascorbate.

DKK1 and Alzheimer's

Alzheimer's disease occurs due to the overproduction of amyloid beta that will cluster together to form amyloid plaques between neurons in the brain and disrupt cell function. In addition, there is an accumulation of neurofibrillary tangles of hyperphosphorylated tau inside the neuron. The Wnt signaling pathway is crucial for brain development processes, which include neuron proliferation and differentiation as well as neuroblast migration and axon guidance. Downregulation of this signaling has been shown in those with Alzheimer's as a result of high levels of DKK1. Because of the hyperphosphorylation induced by DKK1, tau cannot interact with neuronal microtubules consequently compromising axonal transport resulting in synaptic loss and neuronal apoptosis. Because of its antagonistic effects on the Wnt signaling pathway, it is believed that DKK1 is a common marker for neuronal death in neurodegenerative diseases like Alzheimer's.

References

References

  1. "Entrez Gene: DKK1 dickkopf homolog 1 (Xenopus laevis)".
  2. (1999). "Spatially distinct head and heart inducers within the Xenopus organizer region". Current Biology.
  3. (September 2001). "Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse". Developmental Cell.
  4. (May 2008). "Dkk1 and Wnt3 interact to control head morphogenesis in the mouse". Development.
  5. (February 2001). "Wnt antagonism initiates cardiogenesis in Xenopus laevis". Genes & Development.
  6. (June 2001). "Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6". Current Biology.
  7. (April 2008). "The functions and possible significance of Kremen as the gatekeeper of Wnt signalling in development and pathology". Journal of Cellular and Molecular Medicine.
  8. (2019-01-30). "The role of sclerostin and dickkopf-1 in oral tissues - A review from the perspective of the dental disciplines". F1000Research.
  9. (October 2012). "Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases". Endocrine Reviews.
  10. (February 2010). "Dickkopf-1 as a potential therapeutic target in Paget's disease of bone". Expert Opinion on Therapeutic Targets.
  11. (February 2008). "Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes". The Journal of Investigative Dermatology.
  12. (October 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.
  13. (April 2009). "Wnt signaling in Alzheimer's disease: up or down, that is the question". Ageing Research Reviews.
  14. (September 2018). "Dickkopf-1: Current knowledge and related diseases". Life Sciences.

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