Naked cuticle 1

Last updated

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

  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

Related Research Articles

<span class="mw-page-title-main">Paracrine signaling</span> Form of localized cell signaling

In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance, as opposed to cell signaling by endocrine factors, hormones which travel considerably longer distances via the circulatory system; juxtacrine interactions; and autocrine signaling. Cells that produce paracrine factors secrete them into the immediate extracellular environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain.

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 is a portmanteau created from the names Wingless and Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans.

<span class="mw-page-title-main">Catenin</span>

Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells. The first two catenins that were identified became known as α-catenin and β-catenin. α-Catenin can bind to β-catenin and can also bind filamentous actin (F-actin). β-Catenin binds directly to the cytoplasmic tail of classical cadherins. Additional catenins such as γ-catenin and δ-catenin have been identified. The name "catenin" was originally selected because it was suspected that catenins might link cadherins to the cytoskeleton.

<span class="mw-page-title-main">Adenomatous polyposis coli</span> Protein-coding gene in the species Homo sapiens

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 negative regulator that controls beta-catenin concentrations and interacts with E-cadherin, which are involved in cell adhesion. Mutations in the APC gene may result in colorectal cancer and desmoid tumors.

<span class="mw-page-title-main">Catenin beta-1</span> Mammalian protein found in Homo sapiens

Catenin beta-1, also known as β-catenin (beta-catenin), is a protein that in humans is encoded by the CTNNB1 gene.

<span class="mw-page-title-main">AXIN1</span> Protein-coding gene in the species Homo sapiens

Axin-1 is a protein that in humans is encoded by the AXIN1 gene.

<span class="mw-page-title-main">Proto-oncogene Wnt-1</span> Protein-coding gene in the species Homo sapiens

Proto-oncogene Wnt-1, or Proto-oncogene Int-1 homolog is a protein that in humans is encoded by the WNT1 gene.

<span class="mw-page-title-main">DVL1</span> Human protein and coding gene

Segment polarity protein dishevelled homolog DVL-1 is a protein that in humans is encoded by the DVL1 gene.

<span class="mw-page-title-main">Secreted frizzled-related protein 1</span> Protein-coding gene in the species Homo sapiens

Secreted frizzled-related protein 1, also known as SFRP1, is a protein which in humans is encoded by the SFRP1 gene.

<span class="mw-page-title-main">LRP6</span> Protein-coding gene in the species Homo sapiens

Low-density lipoprotein receptor-related protein 6 is a protein that in humans is encoded by the LRP6 gene. LRP6 is a key component of the LRP5/LRP6/Frizzled co-receptor group that is involved in canonical Wnt pathway.

<span class="mw-page-title-main">WNT3A</span> Protein-coding gene in the species Homo sapiens

Protein Wnt-3a is a protein that in humans is encoded by the WNT3A gene.

<span class="mw-page-title-main">AXIN2</span> Protein-coding gene in the species Homo sapiens

Axin-2, also known as axin-like protein (Axil), axis inhibition protein 2 (AXIN2), or conductin, is a protein that in humans is encoded by the AXIN2 gene.

<span class="mw-page-title-main">DVL2</span> Human protein and coding gene

Segment polarity protein dishevelled homolog DVL-2 is a protein that in humans is encoded by the DVL2 gene.

<span class="mw-page-title-main">DVL3</span> Protein-coding gene in the species Homo sapiens

Segment polarity protein dishevelled homolog DVL-3 is a protein that in humans is encoded by the DVL3 gene.

<span class="mw-page-title-main">Dishevelled</span> Family of proteins

Dishevelled (Dsh) is a family of proteins involved in canonical and non-canonical Wnt signalling pathways. Dsh is a cytoplasmic phosphoprotein that acts directly downstream of frizzled receptors. It takes its name from its initial discovery in flies, where a mutation in the dishevelled gene was observed to cause improper orientation of body and wing hairs. There are vertebrate homologs in zebrafish, Xenopus (Xdsh), mice and humans. Dsh relays complex Wnt signals in tissues and cells, in normal and abnormal contexts. It is thought to interact with the SPATS1 protein when regulating the Wnt Signalling pathway.

The Nodal signaling pathway is a signal transduction pathway important in regional and cellular differentiation during embryonic development.

<span class="mw-page-title-main">TCF/LEF family</span> Group of genes

The TCF/LEF family is a group of genes that encode transcription factors which bind to DNA through a SOX-like high mobility group domain. They are involved in the Wnt signaling pathway, particularly during embryonic and stem-cell development, but also had been found to play a role in cancer and diabetes. TCF/LEF factors recruit the coactivator beta-catenin to enhancer elements of genes they target. They can also recruit members of the Groucho family of corepressors.

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, but only Nkd2 can bind to the EGF-ligand family member TGF alpha and regulate its polarized secretion in cultured epithelial cells.

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 screens for pattern-formation mutants in the fruit fly Drosophila melanogaster. The Nkd gene family was first cloned in the laboratory of Matthew P. Scott. Like many cleverly named fly mutants, the name "naked cuticle" derives from the fact that mutants lack most of the hair-like protrusions from their ventral cuticle and thus appear "naked".

In molecular biology, the protein domain, WIF N-terminal refers to the N terminal domain of the protein, WIF. It stands for, Wnt-inhibitory factor, whereby wnt is a signalling molecule also known as wingless. Wnt is a molecule in the wnt signaling pathway. The WIF domain binds to the wnt ligand since it inhibits it.