SNAI2

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SNAI2
Identifiers
Aliases SNAI2, SLUG, SLUGH1, SNAIL2, WS2D, snail family transcriptional repressor 2, SLUGH
External IDs MGI: 1096393 HomoloGene: 31127 GeneCards: SNAI2
RNA expression pattern
PBB GE SNAI2 213139 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003068

NM_011415

RefSeq (protein)

NP_003059

NP_035545

Location (UCSC) Chr 8: 48.92 – 48.92 Mb Chr 16: 14.71 – 14.71 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Zinc finger protein SNAI2 is a protein that in humans is encoded by the SNAI2 gene.[3][4][5]

Function[edit]

This gene encodes a member of the Snail superfamily of C2H2-type zinc finger transcription factors. The encoded protein acts as a transcriptional repressor that binds to E-box motifs and is also likely to repress E-cadherin transcription in breast carcinoma. This protein is involved in epithelial-mesenchymal transitions and has antiapoptotic activity. It regulates differentiation and migration of neural crest cells along with other genes (e.g. FOXD3, SOX9 and SOX10, BMPs) in embryonic life. Mutations in this gene may be associated with sporadic cases of neural tube defects.[5]

Function[edit]

The human embryonic protein SNAI2, commonly known as SLUG, is a zinc finger transcriptional repressor which downregulates expression of E-cadherin in premigratory neural crest cells; thus, SNAI2 induces tightly bound epithelial cells to break into a loose mesenchymal phenotype, allowing gastrulation of mesoderm in the developing embryo.[6][7] Structurally similar to anti-apoptotic Ces-1 in C. elegans, SLUG is a negative regulator of productive cell death in the developing embryo and adults.[6][8]

Clinical significance[edit]

Widely expressed in human tissues, SLUG is most notably absent in peripheral blood leukocytes, adult liver, and both fetal and adult brain tissues.[8] SLUG plays a role in breast carcinoma as well as leukemia by downregulation of E-cadherin, which supports mesenchymal phenotype by shifting expression from a Type I to Type II cadherin profile.[8][9] Maintenance of mesenchymal phenotype enables metastasis of tumor cells, though SLUG is expressed in carcinomas regardless to invasiveness.[6][7][8] A knockout model using chick embryos has also showed inhibition of mesodermal and neural crest delamination; chick embryo Slug gain of function appears to increase neural crest production.[6] Mutations in Slug are associated with loss of pregnancy during gastrulation in some animals.[6]

Interactions[edit]

BMPs precede expression of SLUG, and are suspected as the immediate upstream inducers of gene expression.[7][10]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Rhim H, Savagner P, Thibaudeau G, Thiery JP, Pavan WJ (Jan 1998). "Localization of a neural crest transcription factor, Slug, to mouse chromosome 16 and human chromosome 8". Mammalian Genome. 8 (11): 872–3. PMID 9337409. doi:10.1007/s003359900601. 
  4. ^ Cohen ME, Yin M, Paznekas WA, Schertzer M, Wood S, Jabs EW (August 1998). "Human SLUG gene organization, expression, and chromosome map location on 8q". Genomics. 51 (3): 468–71. PMID 9721220. doi:10.1006/geno.1998.5367. 
  5. ^ a b "Entrez Gene: SNAI2 snail homolog 2 (Drosophila)". 
  6. ^ a b c d e Nieto MA (March 2002). "The snail superfamily of zinc-finger transcription factors". Nature Reviews Molecular Cell Biology. 3 (3): 155–66. PMID 11994736. doi:10.1038/nrm757. 
  7. ^ a b c Carlson BM (2013). Human Embryology and Developmental Biology (5th ed.). Philadelphia, PA: Elsevier Health Sciences. pp. 101–102, 106, 313, 362, 382. ISBN 978-1-4557-2794-0. 
  8. ^ a b c d Inukai T, Inoue A, Kurosawa H, Goi K, Shinjyo T, Ozawa K, Mao M, Inaba T, Look AT (September 1999). "SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein". Molecular Cell. 4 (3): 343–52. PMID 10518215. doi:10.1016/S1097-2765(00)80336-6. 
  9. ^ Kalluri R, Weinberg RA (June 2009). "The basics of epithelial-mesenchymal transition". The Journal of Clinical Investigation. 119 (6): 1420–8. PMC 2689101Freely accessible. PMID 19487818. doi:10.1172/jci39104. 
  10. ^ Sakai D, Wakamatsu Y (2005). "Regulatory mechanisms for neural crest formation". Cells, Tissues, Organs. 179 (1-2): 24–35. PMID 15942190. doi:10.1159/000084506. 

Further reading[edit]