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 fu ...
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
Gastrulation is the stage in the early embryonic development of most animals, during which the blastula (a single-layered hollow sphere of cells), or in mammals the blastocyst is reorganized into a multilayered structure known as the gastrula. ...
.
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 fu ...
s. The encoded protein acts as a
transcriptional repressor that binds to
E-box 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 ovari ...
transcription in breast carcinoma. This protein is involved in
epithelial-mesenchymal transitions and has
antiapoptotic
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes includ ...
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, ...
cells along with other genes (e.g.
FOXD3
Forkhead box D3 also known as FOXD3 is a forkhead protein that in humans is encoded by the ''FOXD3'' gene.
Function
This gene belongs to the forkhead protein family of transcription factors which is characterized by a DNA-binding forkhead do ...
,
SOX9
Transcription factor SOX-9 is a protein that in humans is encoded by the ''SOX9'' gene.
Function
SOX-9 recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins. It is expressed by proliferating but n ...
and
SOX10,
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
The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical Emb ...
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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