SNAI2

SNAI2

SNAI2

Protein

Zinc finger protein SNAI2 is a transcription factor that in humans is encoded by the SNAI2 gene. It promotes the differentiation and migration of certain cells and has roles in initiating gastrulation.[5][6][7]

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Function

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.[7][8]

SNAI2 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.[9][10] 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.[9][11]

Clinical significance

Widely expressed in human tissues, SLUG is most notably absent in peripheral blood leukocytes, adult liver, and both fetal and adult brain tissues.[11] 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.[11][12] Maintenance of mesenchymal phenotype enables metastasis of tumor cells, though SLUG is expressed in carcinomas regardless to invasiveness.[9][10][11] 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.[9] Mutations in Slug are associated with loss of pregnancy during gastrulation in some animals.[9]

Interactions

BMPs precede expression of SLUG, and are suspected as the immediate upstream inducers of gene expression.[10][13]

References

  1. [1]
    GRCh38: Ensembl release 89: ENSG00000019549 – Ensembl, May 2017
  2. [2]
    GRCm38: Ensembl release 89: ENSMUSG00000022676 – Ensembl, May 2017
  3. [3]
    "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. [4]
    "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. [5]
    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. doi:10.1007/s003359900601. PMID 9337409. S2CID 2177885.
  6. [6]
    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. doi:10.1006/geno.1998.5367. PMID 9721220.
  7. [7]
    "Entrez Gene: SNAI2 snail homolog 2 (Drosophila)".
  8. [8]
    Stegmann, K.; Boecker, J.; Kosan, C.; Ermert, A.; Kunz, J.; Koch, M. C. (August 1999). "Human transcription factor SLUG: mutation analysis in patients with neural tube defects and identification of a missense mutation (D119E) in the Slug subfamily-defining region". Mutation Research. 406 (2–4): 63–69. doi:10.1016/s1383-5726(99)00002-3. ISSN 0027-5107. PMID 10479723.
  9. [9]
    Nieto MA (March 2002). "The snail superfamily of zinc-finger transcription factors". Nature Reviews Molecular Cell Biology. 3 (3): 155–66. doi:10.1038/nrm757. PMID 11994736. S2CID 8330951.
  10. [10]
    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.
  11. [11]
    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. doi:10.1016/S1097-2765(00)80336-6. PMID 10518215.
  12. [12]
    Kalluri R, Weinberg RA (June 2009). "The basics of epithelial-mesenchymal transition". The Journal of Clinical Investigation. 119 (6): 1420–8. doi:10.1172/jci39104. PMC 2689101. PMID 19487818.
  13. [13]
    Sakai D, Wakamatsu Y (2005). "Regulatory mechanisms for neural crest formation". Cells Tissues Organs. 179 (1–2): 24–35. doi:10.1159/000084506. PMID 15942190. S2CID 1886380.

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