SOX10
Transkripcijski faktor SOX-10 jest protein koji je kod ljudi kodiran genom SOX10 sa hromosoma 22.[5][6][7][8]
Aminokiselinska sekvenca
[uredi | uredi izvor]Dužina polipeptidnog lanca je 466 aminokiselina, a molekulska težina 49.911 Da.[8]
10 | 20 | 30 | 40 | 50 | ||||
---|---|---|---|---|---|---|---|---|
MAEEQDLSEV | ELSPVGSEEP | RCLSPGSAPS | LGPDGGGGGS | GLRASPGPGE | ||||
LGKVKKEQQD | GEADDDKFPV | CIREAVSQVL | SGYDWTLVPM | PVRVNGASKS | ||||
KPHVKRPMNA | FMVWAQAARR | KLADQYPHLH | NAELSKTLGK | LWRLLNESDK | ||||
RPFIEEAERL | RMQHKKDHPD | YKYQPRRRKN | GKAAQGEAEC | PGGEAEQGGT | ||||
AAIQAHYKSA | HLDHRHPGEG | SPMSDGNPEH | PSGQSHGPPT | PPTTPKTELQ | ||||
SGKADPKRDG | RSMGEGGKPH | IDFGNVDIGE | ISHEVMSNME | TFDVAELDQY | ||||
LPPNGHPGHV | SSYSAAGYGL | GSALAVASGH | SAWISKPPGV | ALPTVSPPGV | ||||
DAKAQVKTET | AGPQGPPHYT | DQPSTSQIAY | TSLSLPHYGS | AFPSISRPQF | ||||
DYSDHQPSGP | YYGHSGQASG | LYSAFSYMGP | SQRPLYTAIS | DPSPSGPQSH | ||||
SPTHWEQPVY | TTLSRP |
Funkcija
[uredi | uredi izvor]Ovaj gen kodira člana porodice SOX (srodne SRY-u HMG-kutije) porodice faktora transkripcije uključenih u regulaciju i razvoja embriona i određivanje ćelijske sudbine. Kodirani protein djeluje kao transkripcijski aktivator nakon formiranja proteinskog kompleksa s drugim proteinima. Ovaj protein djeluje kao nukleocitoplazmatski šatl-protein i važan je za razvoj nervnog grebena i perifernog nervnog sistema.[8]
U melanocitnim ćelijama, postoje dokazi da ekspresija gena SOX10 može biti regulirana transkripcijskim faktorom povezanim sa mikroftalmijom (MITF).[9]
Mutacije
[uredi | uredi izvor]Mutacije ovog gena povezane su sa Waardenburg-Shahovim sindromom[8] i uveinim melanomom.[10]
Imunobojenje
[uredi | uredi izvor]SOX10 se koristi kao imunohistohemijski marker, jer je pozitivan na:[11]
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Imunohistohemijski nalaz SOX10 u dermnom nevusu ima pozitivno obojene ćelije nevusa (strelice)
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folikulima dlake][].
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Imunohistohemijska obrada SOX10 olakšava prikaz lentigo maligna, kao povećanog broja melanocita duž stratum basale i jedarnog plejomorfizma. Promjene su kontinuirane sa resekcijskom marginom (obilježeno žutom bojom, lijevo), što daje dijagnozu neradikalno uklonjenog lentigo maligna.
Interakcije
[uredi | uredi izvor]Interakcija između SOX10 i PAX3 proučavana je najbolje kod pacijenata sa Waardenburgovim sindromom, autosomno dominantnim poremećajem koji je podijeljen u četiri različita tipa, na osnovu mutacije u dodatnim genima. Smatra se da su interakcije SOX10 i PAX3 regulatori drugih gena uključenih u simptome Waardenburgovog sindroma, posebno MITF, koji utiče na razvoj melanocita, kao i formiranje nervnog grebena. Ekspresija MITF može se transaktivirati pomoću SOX10 i PAX3, da bi imao aditivni efekt.[12][13] Dva gena imaju međusomno bliska vezujuća mjesta na uzvodnom pojačivaču gena c-RET.[14] Također se smatra da SOX10 cilja na dopahrom-tautomerazu preko sinergijske interakcije sa MITF-om, što onda rezultira drugim promjenama melanocita.[15]
SOX10 može uticati na stvaranje transkripcije mijelinskih proteina putem njegove interakcije sa proteinima kao što su OLIG1 i EGR2,[16][17] što je važno za funkcionalnost neurona. Identificirani su i ostali kofaktori, kao što su SP1, OCT6, NMI, FOXD3 i SOX2.[18]
Interakcija između SOX10 i NMI javljaju se koeksprimirano u glijinim ćelijamama, gliomima i kičmenoj moždini i pokazalo se da modulira transkripcijsku aktivnost SOX10.[19]
Također pogledajte
[uredi | uredi izvor]Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000100146 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033006 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Pingault V, Bondurand N, Kuhlbrodt K, Goerich DE, Préhu MO, Puliti A, Herbarth B, Hermans-Borgmeyer I, Legius E, Matthijs G, Amiel J, Lyonnet S, Ceccherini I, Romeo G, Smith JC, Read AP, Wegner M, Goossens M (Feb 1998). "SOX10 mutations in patients with Waardenburg-Hirschsprung disease". Nature Genetics. 18 (2): 171–3. doi:10.1038/ng0298-171. PMID 9462749. S2CID 2327032.
- ^ Bondurand N, Kuhlbrodt K, Pingault V, Enderich J, Sajus M, Tommerup N, Warburg M, Hennekam RC, Read AP, Wegner M, Goossens M (Sep 1999). "A molecular analysis of the yemenite deaf-blind hypopigmentation syndrome: SOX10 dysfunction causes different neurocristopathies". Human Molecular Genetics. 8 (9): 1785–9. doi:10.1093/hmg/8.9.1785. PMID 10441344.
- ^ Huber WE, Price ER, Widlund HR, Du J, Davis IJ, Wegner M, Fisher DE (Nov 2003). "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. doi:10.1074/jbc.M309036200. PMID 12944398.
- ^ a b c d "Entrez Gene: SOX10 SRY (sex determining region Y)-box 10".
- ^ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
- ^ Das D, Kaur I, Ali MJ, Biswas NK, Das S, Kumar S, Honavar SG, Maitra A, Chakrabarti S, Majumder PP (Jul 2014). "Exome sequencing reveals the likely involvement of SOX10 in uveal melanoma". Optometry and Vision Science. 91 (7): e185–92. doi:10.1097/OPX.0000000000000309. PMID 24927141. S2CID 24239911.
- ^ Nat Pernick. "Stains - SOX10". Pathology Outlines. Topic Completed: 1 February 2014. Revised: 20 September 2019
- ^ Potterf SB, Furumura M, Dunn KJ, Arnheiter H, Pavan WJ (July 2000). "Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3". Hum. Genet. 107 (1): 1–6. doi:10.1007/s004390000328. PMID 10982026. S2CID 24931810.
- ^ Bondurand N, Pingault V, Goerich DE, Lemort N, Le Caignec C, Wegner M, Goossens M (August 2000). "Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome". Hum. Mol. Genet. 9 (13): 1907–17. doi:10.1093/hmg/9.13.1907. PMID 10942418.
- ^ Lang D, Epstein JA (April 2003). "Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer". Hum. Mol. Genet. 12 (8): 937–45. doi:10.1093/hmg/ddg107. PMID 12668617.
- ^ Ludwig A, Rehberg S, Wegner, M (January 2004). "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. doi:10.1016/s0014-5793(03)01446-7. PMID 14706856. S2CID 8245142.
- ^ Li H, Lu Y, Smith HK, Richardson W (December 2007). "Olig1 and Sox10 Interact Synergistically to Drive Myelin Basic Protein Transcription in Oligodendrocytes". The Journal of Neuroscience. 27 (52): 14375–82. doi:10.1523/jneurosci.4456-07.2007. PMC 6329447. PMID 18160645.
- ^ LeBlanc S, Ward R, Svaren, J (May 2007). "Neuropathy-Associated Egr2 Mutants Disrupt Cooperative Activation of Myelin Protein Zero by Egr2 and Sox10". Mol. Cell. Biol. 27 (9): 3521–29. doi:10.1128/mcb.01689-06. PMC 1899967. PMID 17325040.
- ^ Bondurand N, Sham MH (October 2013). "The role of SOX10 during enteric nervous system development". Dev. Biol. 382 (1): 330–43. doi:10.1016/j.ydbio.2013.04.024. PMID 23644063.
- ^ Schlierf B, Lang S, Kosian T, Werner T, Wegner M (November 2011). "The high-mobility group transcription factor Sox10 interacts with the N-myc-interacting protein Nmi". J. Mol. Biol. 353 (5): 1033–42. doi:10.1016/j.jmb.2005.09.013. PMID 16214168.
Dopunska literatura
[uredi | uredi izvor]- Jacobs JM, Wilson J (1992). "An unusual demyelinating neuropathy in a patient with Waardenburg's syndrome". Acta Neuropathol. 83 (6): 670–4. doi:10.1007/BF00299420. PMID 1636383. S2CID 35774306.
- Southard-Smith EM, Kos L, Pavan WJ (1998). "Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model". Nat. Genet. 18 (1): 60–4. doi:10.1038/ng0198-60. PMID 9425902. S2CID 25574343.
- Kuhlbrodt K, Schmidt C, Sock E, Pingault V, Bondurand N, Goossens M, Wegner M (1998). "Functional analysis of Sox10 mutations found in human Waardenburg-Hirschsprung patients". J. Biol. Chem. 273 (36): 23033–8. doi:10.1074/jbc.273.36.23033. PMID 9722528.
- Pusch C, Hustert E, Pfeifer D, Südbeck P, Kist R, Roe B, Wang Z, Balling R, Blin N, Scherer G (1998). "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. doi:10.1007/s004390050793. PMID 9760192. S2CID 20623767.
- Inoue K, Tanabe Y, Lupski JR (1999). "Myelin deficiencies in both the central and the peripheral nervous systems associated with a SOX10 mutation". Ann. Neurol. 46 (3): 313–8. doi:10.1002/1531-8249(199909)46:3<313::AID-ANA6>3.0.CO;2-7. PMID 10482261.
- 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 (1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. Bibcode:1999Natur.402..489D. doi:10.1038/990031. PMID 10591208.
- 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 (2000). "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. doi:10.1086/302895. PMC 1378013. PMID 10762540.
- Bondurand N, Pingault V, Goerich DE, Lemort N, Sock E, Le Caignec C, Wegner M, Goossens M (2000). "Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome". Hum. Mol. Genet. 9 (13): 1907–17. doi:10.1093/hmg/9.13.1907. PMID 10942418.
- Smit DJ, Smith AG, Parsons PG, Muscat GE, Sturm RA (2000). "Domains of Brn-2 that mediate homodimerization and interaction with general and melanocytic transcription factors". Eur. J. Biochem. 267 (21): 6413–22. doi:10.1046/j.1432-1327.2000.01737.x. PMID 11029584.
- Sham MH, Lui VC, Chen BL, Fu M, Tam PK (2001). "Novel mutations of SOX10 suggest a dominant negative role in Waardenburg-Shah syndrome". J. Med. Genet. 38 (9): 30e–30. doi:10.1136/jmg.38.9.e30. PMC 1734934. PMID 11546831.
- Rehberg S, Lischka P, Glaser G, Stamminger T, Wegner M, Rosorius O (2002). "Sox10 is an active nucleocytoplasmic shuttle protein, and shuttling is crucial for Sox10-mediated transactivation". Mol. Cell. Biol. 22 (16): 5826–34. doi:10.1128/MCB.22.16.5826-5834.2002. PMC 133963. PMID 12138193.
- Pingault V, Girard M, Bondurand N, Dorkins H, Van Maldergem L, Mowat D, Shimotake T, Verma I, Baumann C, Goossens M (2002). "SOX10 mutations in chronic intestinal pseudo-obstruction suggest a complex physiopathological mechanism". Hum. Genet. 111 (2): 198–206. doi:10.1007/s00439-002-0765-8. PMID 12189494. S2CID 2292165.
- Lang D, Epstein JA (2003). "Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer". Hum. Mol. Genet. 12 (8): 937–45. doi:10.1093/hmg/ddg107. PMID 12668617.
- Shimotake T, Tomiyama H, Aoi S, Iwai N (2003). "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. doi:10.1016/jpsu.2003.50186. PMID 12720173.
- Chan KK, Wong CK, Lui VC, Tam PK, Sham MH (2003). "Analysis of SOX10 mutations identified in Waardenburg-Hirschsprung patients: Differential effects on target gene regulation". J. Cell. Biochem. 90 (3): 573–85. doi:10.1002/jcb.10656. PMID 14523991. S2CID 22751147.
- Inoue K, Khajavi M, Ohyama T, Hirabayashi S, Wilson J, Reggin JD, Mancias P, Butler IJ, Wilkinson MF, Wegner M, Lupski JR (2004). "Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations". Nat. Genet. 36 (4): 361–9. doi:10.1038/ng1322. PMID 15004559.
Vanjski linkovi
[uredi | uredi izvor]- SOX10 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)
Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.