Disease relevance of DKK2

• DKK2 mRNA was expressed in Ewing's sarcoma, and fetal heart [1].
• These results suggest that DKK2 inhibits renal cancer progression through apoptotic and cell cycle pathways [2].

High impact information on DKK2

• Furthermore, the expression of several CUTL1 target genes involved in proliferation and migration, such as DNA polymerase A and DKK2, was modulated by PKA-induced phosphorylation [3].
• We show that Dkk1, unlike Dkk2, negatively regulates osteoblast differentiation and bone formation [4].
• The related Dkk2, however, can function either as LRP6 agonist or antagonist, depending on the cellular context, suggesting that its activity is modulated by unknown co-factors [5].
• We have recently identified the transmembrane proteins Kremen1 and -2 as additional Dkk receptors, which bind to both Dkk1 and Dkk2 with high affinity [5].
• The Notch-DKK2 signaling loop, created or potentiated in primates, was complementary to WNT-DKK1 and BMP-IHH-SFRP1 signaling loops for negative regulation of canonical WNT signaling pathway [6].

Biological context of DKK2

• Double NREs were identified within human DKK2 promoter by bioinformatics and human intelligence (Humint) [6].
• Because DKK2 is a key player in the stem cell signaling network, the DKK2 gene at human chromosome 4q25 is a candidate tumor suppressor gene inactivated due to epigenetic silencing and/or deletion [6].
• Comparative genomics on DKK2 and DKK4 orthologs [1].
• TATA-box was identified within Dkk2 and Dkk4 promoters [1].

Anatomical context of DKK2

• The human DKK2 gene was characterized as Notch signaling target in intestinal stem cells [6].
• Unexpectedly, the Wnt antagonist Dkk2 is required for terminal osteoblast differentiation and mineralized matrix formation [4].

Associations of DKK2 with chemical compounds

• Asn-linked glycosylation site at codon 52 was conserved among mammalian Dkk2 orthologs; however, Asn-linked glycosylation site was not identified among mammalian Dkk4 orthologs [1].

Other interactions of DKK2

• Dkk3 and Dkk2 expression was also concentrated at crypt bases [7].

References