Zinc finger protein SNAI2 is a
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
that in humans is encoded by the ''SNAI2''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
. It promotes the differentiation and migration of certain cells and has roles in initiating
gastrulation.
Function
This gene encodes a member of the Snail superfamily of C2H2-type
zinc finger
A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struct ...
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
s. The encoded protein acts as a
transcriptional repressor that binds to
E-box An E-box (enhancer box) is a DNA response element found in some eukaryotes that acts as a protein-binding site and has been found to regulate gene expression in neurons, muscles, and other tissues. Its specific DNA sequence, CANNTG (where N can b ...
motifs and is also likely to repress
E-cadherin
Cadherin-1 or Epithelial cadherin (E-cadherin), (not to be confused with the APC/C activator protein CDH1) is a protein that in humans is encoded by the ''CDH1'' gene. Mutations are correlated with gastric, breast, colorectal, thyroid, and ovarian ...
transcription in breast carcinoma. This protein is involved in
epithelial-mesenchymal transitions and has
antiapoptotic activity. It regulates differentiation and migration of
neural crest
Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...
cells along with other genes (e.g.
FOXD3,
SOX9 and
SOX10
Transcription factor SOX-10 is a protein that in humans is encoded by the ''SOX10'' gene.
Function
This gene encodes a member of the SOX gene family, SOX (Testis-determining factor, SRY-related HMG-box) family of transcription factors involved ...
,
BMPs) in embryonic life. Mutations in this gene may be associated with sporadic cases of
neural tube
In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural fold become elevated, ...
defects.
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.
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.
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.
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.
Maintenance of mesenchymal phenotype enables metastasis of tumor cells, though SLUG is expressed in carcinomas regardless to invasiveness.
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.
Mutations in Slug are associated with loss of pregnancy during gastrulation in some animals.
Interactions
BMPs precede expression of SLUG, and are suspected as the immediate upstream inducers of gene expression.
References
Further reading
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