Biology:SOX10
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Transcription factor SOX-10 is a protein that in humans is encoded by the SOX10 gene.[1][2][3][4]
Function
This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and determination of cell fate. The encoded protein acts as a transcriptional activator after forming a protein complex with other proteins. This protein acts as a nucleocytoplasmic shuttle protein and is important for neural crest and peripheral nervous system development.[4]
In melanocytic cells, there is evidence that SOX10 gene expression may be regulated by MITF.[5]
Mutations
Mutations in this gene are associated with Waardenburg–Shah syndrome[4] and uveal melanoma.[6]
Immunostain
SOX10 is used as an immunohistochemistry marker, being positive in:[7]
- Neuroectodermal neoplasms of neural crest origin, especially:
- Melanoma, although desmoplastic melanomas may be only focally positive.
- Nevus
SOX10 immunohistochemistry in a dermal nevus, showing positively staining nevus cells (arrows)
SOX10 immunohistochemistry of normal skin (top) and atypical melanocytic proliferation (bottom), seen mainly in hair follicles.
SOX10 immunohistochemistry facilitates showing lentigo maligna, as an increased number of melanocytes along stratum basale and nuclear pleumorphism. The changes are continuous with the resection margin (inked in yellow, at left), conferring a diagnosis of a not radically removed lentigo maligna.
Interactions
The interaction between SOX10 and PAX3 is studied best in human patients with Waardenburg syndrome, an autosomal dominant 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 MITF, which influences the development of melanocytes as well as neural crest formation. MITF expression can be transactivated by both SOX10 and PAX3 to have an additive effect.[8][9] The two genes have binding sites near one another on the upstream enhancer of the c-RET gene.[10] SOX10 is also thought to target dopachrome tautomerase through a synergistic interaction with MITF, which then results in other melanocyte alteration.[11]
SOX10 can influence the generation of Myelin Protein Zero (MPZ) transcription through its interactions with proteins such as OLIG1 and EGR2,[12][13] which is important for the functionality of neurons. Other cofactors have been identified, such as SP1, OCT6, NMI, FOXD3 and SOX2.[14]
The interaction between SOX10 and NMI seems to be coexpressed in glial cells, gliomas, and the spinal cord and has been shown to modulate the transcriptional activity of SOX10.[15]
See also
- SOX genes
- List of histologic stains that aid in diagnosis of cutaneous conditions
References
- ↑ "SOX10 mutations in patients with Waardenburg-Hirschsprung disease". Nature Genetics 18 (2): 171–3. Feb 1998. doi:10.1038/ng0298-171. PMID 9462749.
- ↑ "A molecular analysis of the yemenite deaf-blind hypopigmentation syndrome: SOX10 dysfunction causes different neurocristopathies". Human Molecular Genetics 8 (9): 1785–9. Sep 1999. doi:10.1093/hmg/8.9.1785. PMID 10441344.
- ↑ "A tissue-restricted cAMP transcriptional response: SOX10 modulates alpha-melanocyte-stimulating hormone-triggered expression of microphthalmia-associated transcription factor in melanocytes". The Journal of Biological Chemistry 278 (46): 45224–30. Nov 2003. doi:10.1074/jbc.M309036200. PMID 12944398.
- ↑ 4.0 4.1 4.2 "Entrez Gene: SOX10 SRY (sex determining region Y)-box 10". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6663.
- ↑ "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research 21 (6): 665–76. Dec 2008. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
- ↑ "Exome sequencing reveals the likely involvement of SOX10 in uveal melanoma". Optometry and Vision Science 91 (7): e185–92. Jul 2014. doi:10.1097/OPX.0000000000000309. PMID 24927141.
- ↑ Nat Pernick. "Stains - SOX10". http://www.pathologyoutlines.com/topic/stainssox10.html. Topic Completed: 1 February 2014. Revised: 20 September 2019
- ↑ "Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3". Hum. Genet. 107 (1): 1–6. July 2000. doi:10.1007/s004390000328. PMID 10982026.
- ↑ "Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome". Hum. Mol. Genet. 9 (13): 1907–17. August 2000. doi:10.1093/hmg/9.13.1907. PMID 10942418.
- ↑ "Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer". Hum. Mol. Genet. 12 (8): 937–45. April 2003. doi:10.1093/hmg/ddg107. PMID 12668617.
- ↑ "Melanocyte-specific expression of dopachrome tautomerase is dependent on synergistic gene activation by the Sox10 and Mitf transcription factors". FEBS Letters 556 (1–3): 236–44. January 2004. doi:10.1016/s0014-5793(03)01446-7. PMID 14706856.
- ↑ "Olig1 and Sox10 Interact Synergistically to Drive Myelin Basic Protein Transcription in Oligodendrocytes". The Journal of Neuroscience 27 (52): 14375–82. December 2007. doi:10.1523/jneurosci.4456-07.2007. PMID 18160645.
- ↑ "Neuropathy-Associated Egr2 Mutants Disrupt Cooperative Activation of Myelin Protein Zero by Egr2 and Sox10". Mol. Cell. Biol. 27 (9): 3521–29. May 2007. doi:10.1128/mcb.01689-06. PMID 17325040.
- ↑ "The role of SOX10 during enteric nervous system development". Dev. Biol. 382 (1): 330–43. October 2013. doi:10.1016/j.ydbio.2013.04.024. PMID 23644063.
- ↑ "The high-mobility group transcription factor Sox10 interacts with the N-myc-interacting protein Nmi". J. Mol. Biol. 353 (5): 1033–42. November 2011. doi:10.1016/j.jmb.2005.09.013. PMID 16214168.
Further reading
- "An unusual demyelinating neuropathy in a patient with Waardenburg's syndrome". Acta Neuropathol. 83 (6): 670–4. 1992. doi:10.1007/BF00299420. PMID 1636383.
- "Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model". Nat. Genet. 18 (1): 60–4. 1998. doi:10.1038/ng0198-60. PMID 9425902. https://zenodo.org/record/1233377.
- "Functional analysis of Sox10 mutations found in human Waardenburg-Hirschsprung patients". J. Biol. Chem. 273 (36): 23033–8. 1998. doi:10.1074/jbc.273.36.23033. PMID 9722528.
- "The SOX10/Sox10 gene from human and mouse: sequence, expression, and transactivation by the encoded HMG domain transcription factor". Hum. Genet. 103 (2): 115–23. 1998. doi:10.1007/s004390050793. PMID 9760192.
- "Myelin deficiencies in both the central and the peripheral nervous systems associated with a SOX10 mutation". Ann. Neurol. 46 (3): 313–8. 1999. doi:10.1002/1531-8249(199909)46:3<313::AID-ANA6>3.0.CO;2-7. PMID 10482261.
- "The DNA sequence of human chromosome 22". Nature 402 (6761): 489–95. 1999. doi:10.1038/990031. PMID 10591208. Bibcode: 1999Natur.402..489D.
- "Neurological phenotype in Waardenburg syndrome type 4 correlates with novel SOX10 truncating mutations and expression in developing brain". Am. J. Hum. Genet. 66 (5): 1496–503. 2000. doi:10.1086/302895. PMID 10762540.
- "Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome". Hum. Mol. Genet. 9 (13): 1907–17. 2000. doi:10.1093/hmg/9.13.1907. PMID 10942418.
- "Domains of Brn-2 that mediate homodimerization and interaction with general and melanocytic transcription factors". Eur. J. Biochem. 267 (21): 6413–22. 2000. doi:10.1046/j.1432-1327.2000.01737.x. PMID 11029584.
- "Novel mutations of SOX10 suggest a dominant negative role in Waardenburg-Shah syndrome". J. Med. Genet. 38 (9): 30e–30. 2001. doi:10.1136/jmg.38.9.e30. PMID 11546831.
- "Sox10 is an active nucleocytoplasmic shuttle protein, and shuttling is crucial for Sox10-mediated transactivation". Mol. Cell. Biol. 22 (16): 5826–34. 2002. doi:10.1128/MCB.22.16.5826-5834.2002. PMID 12138193.
- "SOX10 mutations in chronic intestinal pseudo-obstruction suggest a complex physiopathological mechanism". Hum. Genet. 111 (2): 198–206. 2002. doi:10.1007/s00439-002-0765-8. PMID 12189494.
- "Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer". Hum. Mol. Genet. 12 (8): 937–45. 2003. doi:10.1093/hmg/ddg107. PMID 12668617.
- "Discrepancy between macroscopic and microscopic transitional zones in Hirschsprung's disease with reference to the type of RET/GDNF/SOX10 gene mutation". J. Pediatr. Surg. 38 (5): 698–701. 2003. doi:10.1016/jpsu.2003.50186. PMID 12720173.
- "Analysis of SOX10 mutations identified in Waardenburg-Hirschsprung patients: Differential effects on target gene regulation". J. Cell. Biochem. 90 (3): 573–85. 2003. doi:10.1002/jcb.10656. PMID 14523991.
- "Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations". Nat. Genet. 36 (4): 361–9. 2004. doi:10.1038/ng1322. PMID 15004559.
External links
- SOX10+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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