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]
Sources
^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.
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^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.
PMID11274398
^ Katoh M. Molecular cloning, gene structure, and expression analyses of NKD1 and NKD2. Int J Oncol. 2001 Nov;19(5):963-9.
PMID11604995
^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.
PMID17689523
^ 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.
PMID20858476
^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.
PMID19956716