Naked cuticle 1 (NKD1) is a human gene that encodes the protein Nkd1, a member of the Naked cuticle (Nkd) family of proteins that regulate the Wnt signaling pathway.[1][2][3] Insects typically have a single Nkd gene, whereas there are two Nkd genes, Nkd1 and Nkd2, in most vertebrates studied to date (zebrafish appear to have additional homologous genes such as Nkd3).[4][5] Nkd1 binds to the Dishevelled (Dvl) family of proteins (DVL1, DVL2, DVL3). Specific truncating NKD1 mutations identified in DNA mismatch repair deficient colon cancer that disrupt Nkd1/Dvl binding implicate these mutations as a cause of increased Wnt signaling in a subset of human colon cancers, the majority of which have increased Wnt signaling due to mutations the adenomatous polyposis coli (APC), AXIN2, or rarely the beta-catenin genes.[6]

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  1. ↑ Wharton KA Jr, Zimmermann G, Rousset R, Scott MP. Vertebrate proteins related to Drosophila Naked Cuticle bind Dishevelled and antagonize Wnt signaling. Dev Biol. 2001 Jun 1;234(1):93-106. PMID 11356022
  2. ↑ Yan D, Wallingford JB, Sun TQ, Nelson AM, Sakanaka C, Reinhard C, Harland RM, Fantl WJ, Williams LT. Cell autonomous regulation of multiple Dishevelled-dependent pathways by mammalian Nkd. Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3802-7. PMID 11274398
  3. ↑ Katoh M. Molecular cloning, gene structure, and expression analyses of NKD1 and NKD2. Int J Oncol. 2001 Nov;19(5):963-9. PMID 11604995
  4. ↑ Van Raay TJ, Coffey RJ, Solnica-Krezel L. Zebrafish Naked1 and Naked2 antagonize both canonical and non-canonical Wnt signaling. Dev Biol. 2007 Sep 15;309(2):151-68. Epub 2007 Apr 21. PMID 17689523
  5. ↑ Schneider I, Schneider PN, Derry SW, Lin S, Barton LJ, Westfall T, Slusarski DC. Zebrafish Nkd1 promotes Dvl degradation and is required for left-right patterning. Dev Biol. 2010 Dec 1;348(1):22-33. Epub 2010 Sep 19. PMID 20858476
  6. ↑ Guo J, Cagatay T, Zhou G, Chan CC, Blythe S, Suyama K, Zheng L, Pan K, Qian C, Hamelin R, Thibodeau SN, Klein PS, Wharton KA, Liu W. Mutations in the human naked cuticle homolog NKD1 found in colorectal cancer alter Wnt/Dvl/beta-catenin signaling. PLoS One. 2009 Nov 24;4(11):e7982.PMID 19956716
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