Naked cuticle 1 (NKD1) is a human gene that encodes the protein Nkd1, a member of the
Naked cuticle (Nkd)
Naked cuticle (Nkd) is a conserved family of intracellular proteins encoded in most animal genomes. The original mutants were discovered by 1995 Nobel laureates Christiane Nüsslein-Volhard and Eric F. Wieschaus and colleagues in their genetic sc ...
family of proteins that regulate the
Wnt signaling pathway
In cellular biology, the Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt, pronounced "wint", is a portmanteau created from the ...
. Insects typically have a single Nkd gene, whereas there are two Nkd genes, Nkd1 and
Nkd2
Naked cuticle 2 (NKD2) is a human gene that encodes the protein Nkd2, one of the Naked cuticle (Nkd) family of proteins that regulate the Wnt signaling pathway. Both Nkd1 and Nkd2 proteins can bind to Dishevelled proteins (DVL1
Segment polari ...
, in most vertebrates studied to date (zebrafish appear to have additional homologous genes such as Nkd3). Nkd1 binds to the
Dishevelled
Dishevelled (Dsh) is a family of proteins involved in canonical and non-canonical Wnt signalling pathways. Dsh (Dvl in mammals) is a cytoplasmic phosphoprotein that acts directly downstream of frizzled receptors. It takes its name from its initi ...
(Dvl) family of proteins (
DVL1
Segment polarity protein dishevelled homolog DVL-1 is a protein that in humans is encoded by the ''DVL1'' gene.
Function
DVL1, the human homolog of the ''Drosophila'' dishevelled gene (dsh), encodes a cytoplasmic phosphoprotein that regulate ...
,
DVL2,
DVL3). Specific truncating NKD1 mutations identified in
DNA mismatch repair deficient
colon cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel ...
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
Adenomatous polyposis coli (APC) also known as deleted in polyposis 2.5 (DP2.5) is a protein that in humans is encoded by the ''APC'' gene. The APC protein is a Down-regulation, negative regulator that controls beta-catenin concentrations and i ...
(APC),
AXIN2, or rarely the
beta-catenin
Catenin beta-1, also known as β-catenin (''beta''-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
β-Catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcrip ...
genes.
[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]
Sources
Human proteins