SOX10

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.

In melanocytic cells, there is evidence that SOX10 gene expression may be regulated by MITF.{{cite journal | vauthors = Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell & Melanoma Research | volume = 21 | issue = 6 | pages = 665–76 | date = Dec 2008 | pmid = 19067971 | doi = 10.1111/j.1755-148X.2008.00505.x | doi-access = free }}

Mutations in this gene are associated with Waardenburg–Shah syndrome and uveal melanoma.{{cite journal | vauthors = Das D, Kaur I, Ali MJ, Biswas NK, Das S, Kumar S, Honavar SG, Maitra A, Chakrabarti S, Majumder PP | title = Exome sequencing reveals the likely involvement of SOX10 in uveal melanoma | journal = Optometry and Vision Science | volume = 91 | issue = 7 | pages = e185–92 | date = Jul 2014 | pmid = 24927141 | doi = 10.1097/OPX.0000000000000309 | s2cid = 24239911 }}

SOX10 is used as an immunohistochemistry marker, being positive in:{{cite web|url=http://www.pathologyoutlines.com/topic/stainssox10.html|title=Stains - SOX10|author=Nat Pernick|website=Pathology Outlines}} Topic Completed: 1 February 2014. Revised: 20 September 2019

• Neuroectodermal neoplasms of neural crest origin, especially:

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

:*Nevus

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, 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.

File:Immunohistochemistry stain for SOX10 in a metastatic melanoma to a lymph node.jpg|Immunohistochemistry stain for SOX10 in a poorly differentiated metastatic melanoma to a lymph node, helping in its diagnosis.

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.{{cite journal | vauthors = Potterf SB, Furumura M, Dunn KJ, Arnheiter H, Pavan WJ | title = Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3 | journal = Hum. Genet. | volume = 107 | issue = 1 | pages = 1–6 | date = July 2000 | pmid = 10982026 | doi=10.1007/s004390000328| s2cid = 24931810 }}{{cite journal | vauthors = Bondurand N, Pingault V, Goerich DE, Lemort N, Le Caignec C, Wegner M, Goossens M | title = Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome | journal = Hum. Mol. Genet. | volume = 9 | issue = 13 | pages = 1907–17 | date = August 2000 | pmid = 10942418 | doi=10.1093/hmg/9.13.1907| doi-access = free }} The two genes have binding sites near one another on the upstream enhancer of the c-RET gene.{{cite journal | vauthors = Lang D, Epstein JA | title = Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer | journal = Hum. Mol. Genet. | volume = 12 | issue = 8 | pages = 937–45 | date = April 2003 | pmid = 12668617 | doi = 10.1093/hmg/ddg107 | doi-access = free }} SOX10 is also thought to target dopachrome tautomerase through a synergistic interaction with MITF, which then results in other melanocyte alteration.{{cite journal | vauthors = Ludwig A, Rehberg S, Wegner, M | title = Melanocyte-specific expression of dopachrome tautomerase is dependent on synergistic gene activation by the Sox10 and Mitf transcription factors | journal = FEBS Letters | volume = 556 | issue = 1–3 | pages = 236–44 | date = January 2004 | pmid = 14706856 | doi=10.1016/s0014-5793(03)01446-7| s2cid = 8245142 | doi-access = free | bibcode = 2004FEBSL.556..236L }}

SOX10 can influence the generation of Myelin Protein Zero (MPZ) transcription through its interactions with proteins such as OLIG1 and EGR2,{{cite journal | vauthors = Li H, Lu Y, Smith HK, Richardson W | title = Olig1 and Sox10 Interact Synergistically to Drive Myelin Basic Protein Transcription in Oligodendrocytes | journal = The Journal of Neuroscience | volume = 27 | issue = 52 | pages = 14375–82 | date = December 2007 | pmid = 18160645 | doi=10.1523/jneurosci.4456-07.2007| pmc = 6329447 | doi-access = free }}{{cite journal | vauthors = LeBlanc S, Ward R, Svaren, J | title = Neuropathy-Associated Egr2 Mutants Disrupt Cooperative Activation of Myelin Protein Zero by Egr2 and Sox10 | journal = Mol. Cell. Biol. | volume = 27 | issue = 9 | pages = 3521–29 | date = May 2007 | pmc = 1899967 | doi=10.1128/mcb.01689-06 | pmid=17325040}} which is important for the functionality of neurons. Other cofactors have been identified, such as SP1, OCT6, NMI, FOXD3 and SOX2.{{cite journal | vauthors = Bondurand N, Sham MH | title = The role of SOX10 during enteric nervous system development | journal = Dev. Biol. | volume = 382 | issue = 1 | pages = 330–43 | date = October 2013 | pmid = 23644063 | doi=10.1016/j.ydbio.2013.04.024| doi-access = free }}

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.{{cite journal | vauthors = Schlierf B, Lang S, Kosian T, Werner T, Wegner M | title = The high-mobility group transcription factor Sox10 interacts with the N-myc-interacting protein Nmi | journal = J. Mol. Biol. | volume = 353 | issue = 5 | pages = 1033–42 | date = November 2011 | pmid = 16214168 | doi=10.1016/j.jmb.2005.09.013}}

• SOX genes
• List of histologic stains that aid in diagnosis of cutaneous conditions

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• {{cite journal | vauthors = Jacobs JM, Wilson J | title = An unusual demyelinating neuropathy in a patient with Waardenburg's syndrome | journal = Acta Neuropathol. | volume = 83 | issue = 6 | pages = 670–4 | year = 1992 | pmid = 1636383 | doi = 10.1007/BF00299420 | s2cid = 35774306 }}
• {{cite journal | vauthors = Southard-Smith EM, Kos L, Pavan WJ | title = Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model | journal = Nat. Genet. | volume = 18 | issue = 1 | pages = 60–4 | year = 1998 | pmid = 9425902 | doi = 10.1038/ng0198-60 | s2cid = 25574343 | url = https://zenodo.org/record/1233377 }}
• {{cite journal | vauthors = Kuhlbrodt K, Schmidt C, Sock E, Pingault V, Bondurand N, Goossens M, Wegner M | title = Functional analysis of Sox10 mutations found in human Waardenburg-Hirschsprung patients | journal = J. Biol. Chem. | volume = 273 | issue = 36 | pages = 23033–8 | year = 1998 | pmid = 9722528 | doi = 10.1074/jbc.273.36.23033 | doi-access =free }}
• {{cite journal | vauthors = Pusch C, Hustert E, Pfeifer D, Südbeck P, Kist R, Roe B, Wang Z, Balling R, Blin N, Scherer G | title = The SOX10/Sox10 gene from human and mouse: sequence, expression, and transactivation by the encoded HMG domain transcription factor | journal = Hum. Genet. | volume = 103 | issue = 2 | pages = 115–23 | year = 1998 | pmid = 9760192 | doi = 10.1007/s004390050793 | s2cid = 20623767 }}
• {{cite journal | vauthors = Inoue K, Tanabe Y, Lupski JR | title = Myelin deficiencies in both the central and the peripheral nervous systems associated with a SOX10 mutation | journal = Ann. Neurol. | volume = 46 | issue = 3 | pages = 313–8 | year = 1999 | pmid = 10482261 | doi = 10.1002/1531-8249(199909)46:3<313::AID-ANA6>3.0.CO;2-7 | s2cid = 32618827 }}
• {{cite journal | vauthors = Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP | title = The DNA sequence of human chromosome 22 | journal = Nature | volume = 402 | issue = 6761 | pages = 489–95 | year = 1999 | pmid = 10591208 | doi = 10.1038/990031 | bibcode = 1999Natur.402..489D | doi-access = free }}
• {{cite journal | vauthors = Touraine RL, Attié-Bitach T, Manceau E, Korsch E, Sarda P, Pingault V, Encha-Razavi F, Pelet A, Augé J, Nivelon-Chevallier A, Holschneider AM, Munnes M, Doerfler W, Goossens M, Munnich A, Vekemans M, Lyonnet S | title = Neurological phenotype in Waardenburg syndrome type 4 correlates with novel SOX10 truncating mutations and expression in developing brain | journal = Am. J. Hum. Genet. | volume = 66 | issue = 5 | pages = 1496–503 | year = 2000 | pmid = 10762540 | pmc = 1378013 | doi = 10.1086/302895 }}
• {{cite journal | vauthors = Bondurand N, Pingault V, Goerich DE, Lemort N, Sock E, Le Caignec C, Wegner M, Goossens M | title = Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome | journal = Hum. Mol. Genet. | volume = 9 | issue = 13 | pages = 1907–17 | year = 2000 | pmid = 10942418 | doi = 10.1093/hmg/9.13.1907 | doi-access = free }}
• {{cite journal | vauthors = Smit DJ, Smith AG, Parsons PG, Muscat GE, Sturm RA | title = Domains of Brn-2 that mediate homodimerization and interaction with general and melanocytic transcription factors | journal = Eur. J. Biochem. | volume = 267 | issue = 21 | pages = 6413–22 | year = 2000 | pmid = 11029584 | doi = 10.1046/j.1432-1327.2000.01737.x | doi-access = }}
• {{cite journal | vauthors = Sham MH, Lui VC, Chen BL, Fu M, Tam PK | title = Novel mutations of SOX10 suggest a dominant negative role in Waardenburg-Shah syndrome | journal = J. Med. Genet. | volume = 38 | issue = 9 | pages = 30e–30 | year = 2001 | pmid = 11546831 | pmc = 1734934 | doi = 10.1136/jmg.38.9.e30 }}
• {{cite journal | vauthors = Rehberg S, Lischka P, Glaser G, Stamminger T, Wegner M, Rosorius O | title = Sox10 is an active nucleocytoplasmic shuttle protein, and shuttling is crucial for Sox10-mediated transactivation | journal = Mol. Cell. Biol. | volume = 22 | issue = 16 | pages = 5826–34 | year = 2002 | pmid = 12138193 | pmc = 133963 | doi = 10.1128/MCB.22.16.5826-5834.2002 }}
• {{cite journal | vauthors = Pingault V, Girard M, Bondurand N, Dorkins H, Van Maldergem L, Mowat D, Shimotake T, Verma I, Baumann C, Goossens M | title = SOX10 mutations in chronic intestinal pseudo-obstruction suggest a complex physiopathological mechanism | journal = Hum. Genet. | volume = 111 | issue = 2 | pages = 198–206 | year = 2002 | pmid = 12189494 | doi = 10.1007/s00439-002-0765-8 | s2cid = 2292165 }}
• {{cite journal | vauthors = Lang D, Epstein JA | title = Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer | journal = Hum. Mol. Genet. | volume = 12 | issue = 8 | pages = 937–45 | year = 2003 | pmid = 12668617 | doi = 10.1093/hmg/ddg107 | doi-access = free }}
• {{cite journal | vauthors = Shimotake T, Tomiyama H, Aoi S, Iwai N | title = Discrepancy between macroscopic and microscopic transitional zones in Hirschsprung's disease with reference to the type of RET/GDNF/SOX10 gene mutation | journal = J. Pediatr. Surg. | volume = 38 | issue = 5 | pages = 698–701 | year = 2003 | pmid = 12720173 | doi = 10.1016/jpsu.2003.50186 }}
• {{cite journal | vauthors = Chan KK, Wong CK, Lui VC, Tam PK, Sham MH | title = Analysis of SOX10 mutations identified in Waardenburg-Hirschsprung patients: Differential effects on target gene regulation | journal = J. Cell. Biochem. | volume = 90 | issue = 3 | pages = 573–85 | year = 2003 | pmid = 14523991 | doi = 10.1002/jcb.10656 | s2cid = 22751147 }}
• {{cite journal | vauthors = Inoue K, Khajavi M, Ohyama T, Hirabayashi S, Wilson J, Reggin JD, Mancias P, Butler IJ, Wilkinson MF, Wegner M, Lupski JR | title = Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations | journal = Nat. Genet. | volume = 36 | issue = 4 | pages = 361–9 | year = 2004 | pmid = 15004559 | doi = 10.1038/ng1322 | doi-access = free }}

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• {{MeshName|SOX10+protein,+human}}

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{{Transcription factors|g4}}

Category:Transcription factors