DKK1

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

Function
This gene encodes a protein that is a member of the dickkopf family. It is a secreted protein with two is_associated_with::cysteine rich regions and is involved in embryonic development through its inhibition of the is_associated_with::Wnt signaling pathway. Dickkopf WNT signaling pathway inhibitor 1 (Dkk1) is a protein-coding gene that acts from the anterior visceral is_associated_with::endoderm. The dickkopf protein encoded by DKK1 is an antagonistic inhibitor of the WNT signaling pathway that acts by isolating the is_associated_with::LRP6 co-receptor so that it cannot aid in activating the WNT signaling pathway. This inhibition plays a key role in head and forelimb development during anterior is_associated_with::morphogenesis of the embryo.

Interactions
DKK1 has been shown to interact with is_associated_with::LRP6.

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 is_associated_with::multiple myeloma.

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.

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