Transcription factor SOX-10 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

that in humans is encoded by the ''SOX10''

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 ...

Function

This gene encodes a member of the SOX ( SRY-related

HMG-box In molecular biology, the HMG-box (high mobility group box) is a protein domain which is involved in DNA binding. Structure The structure of the HMG-box domain contains three alpha helices separated by loops (see figure to the right). Function ...

) family of

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 involved in the regulation of

embryonic development An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

and determination of cell fate. The encoded protein acts as a

transcriptional activator A transcriptional activator is a protein (transcription factor) that increases transcription of a gene or set of genes. Activators are considered to have ''positive'' control over gene expression, as they function to promote gene transcription and ...

after forming a

protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain. Protein ...

with other proteins. This protein acts as a nucleocytoplasmic shuttle protein and is important for

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, ...

and

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain a ...

development. In melanocytic cells, there is evidence that SOX10 gene expression may be regulated by

MITF Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the ''MITF'' gene. MITF is a basic helix-loop-helix leucine zipper transcription factor ...

Mutations

Mutations in this gene are associated with

Waardenburg–Shah syndrome Waardenburg syndrome is a group of rare genetic conditions characterised by at least some degree of congenital hearing loss and pigmentation deficiencies, which can include bright blue eyes (or one blue eye and one brown eye), a white foreloc ...

and

uveal melanoma Uveal melanoma is a type of eye cancer in the uvea of the eye. It is traditionally classed as originating in the iris, choroid, and ciliary body, but can also be divided into class I (low metastatic risk) and class II (high metastatic risk). ...

Immunostain

SOX10 is used as an

immunohistochemistry Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to a ...

marker, being positive in: Topic Completed: 1 February 2014. Revised: 20 September 2019 * Neuroectodermal neoplasms of

origin, especially: :* Melanoma, although desmoplastic melanomas may be only focally positive. :*

Nevus Nevus (plural nevi) is a nonspecific medical term for a visible, circumscribed, chronic lesion of the skin or mucosa. The term originates from ''nævus'', which is Latin for "birthmark"; however, a nevus can be either congenital (present at bi ...

File:SOX10 immunohistochemistry in a dermal nevus.jpg, SOX10 immunohistochemistry in a dermal nevus, showing positively staining nevus cells (arrows) File:SOX10 immunohistochemistry of normal skin and atypical melanocytic proliferation.jpg, SOX10 immunohistochemistry of normal skin (top) and atypical melanocytic proliferation (bottom), seen mainly in hair follicles. File:SOX10 immunohistochemistry of lentigo maligna.jpg, SOX10 immunohistochemistry facilitates showing

lentigo maligna Lentigo maligna is where melanocyte cells have become malignant and grow continuously along the stratum basale of the skin, but have not invaded below the epidermis. Lentigo maligna is not the same as lentigo maligna melanoma, as detailed below. It ...

, as an increased number of melanocytes along

stratum basale The ''stratum basale'' (basal layer, sometimes referred to as ''stratum germinativum'') is the deepest layer of the five layers of the epidermis, the external covering of skin in mammals. The ''stratum basale'' is a single layer of columnar or ...

and nuclear pleumorphism. The changes are continuous with the

resection margin A resection margin or surgical margin is the margin of apparently non-tumorous tissue around a tumor that has been surgically removed, called " resected", in surgical oncology. The resection is an attempt to remove a cancer tumor so that no portio ...

(inked in yellow, at left), conferring a diagnosis of a not radically removed lentigo maligna.

Interactions

The

interaction Interaction is action that occurs between two or more objects, with broad use in philosophy and the sciences. It may refer to: Science * Interaction hypothesis, a theory of second language acquisition * Interaction (statistics) * Interaction ...

between SOX10 and

PAX3 The PAX3 (paired box gene 3) gene encodes a member of the paired box or PAX family of transcription factors. The PAX family consists of nine human (PAX1-PAX9) and nine mouse (Pax1-Pax9) members arranged into four subfamilies. Human PAX3 and mouse ...

is studied best in human patients with

Waardenburg syndrome Waardenburg syndrome is a group of rare genetic conditions characterised by at least some degree of congenital hearing loss and pigmentation deficiencies, which can include bright blue eyes (or one blue eye and one brown eye), a white forelock ...

, an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...

disorder that is divided into four different types based upon mutations in additional genes. SOX10 and PAX3 interactions are thought to be regulators of other genes involved in the symptoms of Waardenburg syndrome, particularly

, which influences the development of

melanocyte Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and hear ...

s as well as

formation. MITF expression can be transactivated by both SOX10 and PAX3 to have an additive effect. The two genes have binding sites near one another on the upstream enhancer of the c-RET gene. SOX10 is also thought to target dopachrome tautomerase through a synergistic interaction with MITF, which then results in other melanocyte alteration. SOX10 can influence the generation of ''

Myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be l ...

Protein Zero'' (''MPZ'') transcription through its interactions with proteins such as

OLIG1 Oligodendrocyte transcription factor 1 is a protein that in humans is encoded by the ''OLIG1'' gene. See also * Oligodendrocyte * Transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding fac ...

and EGR2, which is important for the functionality of neurons. Other

cofactors Cofactor may also refer to: * Cofactor (biochemistry), a substance that needs to be present in addition to an enzyme for a certain reaction to be catalysed * A domain parameter in elliptic curve cryptography, defined as the ratio between the orde ...

have been identified, such as SP1, OCT6, NMI, FOXD3 and SOX2. The interaction between SOX10 and NMI seems to be coexpressed in

glial cells Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form mye ...

gliomas A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours. Signs and symptoms ...

, and the spinal cord and has been shown to modulate the transcriptional activity of SOX10.

References

External links

* {{Transcription factors, g4 Transcription factors