Transkripcijski faktor SOX-9 je protein koji kod ljudi kodiran genom SOX9.[5][6]

SOX9
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

4EUW

Identifikatori
AliasiSOX9
Vanjski ID-jeviOMIM: 608160 MGI: 98371 HomoloGene: 294 GeneCards: SOX9
Lokacija gena (čovjek)
Hromosom 17 (čovjek)
Hrom.Hromosom 17 (čovjek)[1]
Hromosom 17 (čovjek)
Genomska lokacija za SOX9
Genomska lokacija za SOX9
Bend17q24.3Početak72,121,020 bp[1]
Kraj72,126,416 bp[1]
Lokacija gena (miš)
Hromosom 11 (miš)
Hrom.Hromosom 11 (miš)[2]
Hromosom 11 (miš)
Genomska lokacija za SOX9
Genomska lokacija za SOX9
Bend11 E2|11 77.27 cMPočetak112,673,050 bp[2]
Kraj112,678,586 bp[2]
Obrazac RNK ekspresije


Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity
GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific
core promoter sequence-specific DNA binding
protein kinase activity
protein kinase A catalytic subunit binding
beta-catenin binding
pre-mRNA intronic binding
chromatin binding
GO:0001948, GO:0016582 vezivanje za proteine
vezivanje sa DNK
sequence-specific DNA binding
GO:0000975 transcription cis-regulatory region binding
bHLH transcription factor binding
GO:0001158 cis-regulatory region sequence-specific DNA binding
protein heterodimerization activity
transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific
GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding
Ćelijska komponenta jedro
transcription regulator complex
nukleoplazma
GO:0009327 makromolekulani kompleks
Biološki proces skeletal system development
cellular response to retinoic acid
bronchus cartilage development
positive regulation of protein phosphorylation
heart valve development
limb bud formation
GO:1903364 positive regulation of protein catabolic process
GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II
ureter morphogenesis
negative regulation of immune system process
chondrocyte development
positive regulation of cell proliferation involved in heart morphogenesis
oligodendrocyte differentiation
chondrocyte hypertrophy
prostate gland development
lung smooth muscle development
mammary gland development
negative regulation of ossification
negative regulation of photoreceptor cell differentiation
cellular response to mechanical stimulus
intrahepatic bile duct development
regulation of cell adhesion
negative regulation of chondrocyte differentiation
positive regulation of mesenchymal cell proliferation
astrocyte fate commitment
positive regulation of chondrocyte differentiation
Spermatogeneza
prostate gland morphogenesis
negative regulation of epithelial cell proliferation
lung epithelial cell differentiation
chondrocyte differentiation involved in endochondral bone morphogenesis
negative regulation of canonical Wnt signaling pathway
endocrine pancreas development
negative regulation of cell population proliferation
regulation of apoptotic process
cellular response to transforming growth factor beta stimulus
negative regulation of mesenchymal cell apoptotic process
chromatin remodeling
negative regulation of myoblast differentiation
positive regulation of branching involved in ureteric bud morphogenesis
cell fate commitment
GO:0009373 regulation of transcription, DNA-templated
epidermal growth factor receptor signaling pathway
ossification
regulation of cell proliferation involved in tissue homeostasis
ureter smooth muscle cell differentiation
ERK1 and ERK2 cascade
notochord development
positive regulation of epithelial cell migration
Sertoli cell differentiation
male sex determination
negative regulation of gene expression
transcription, DNA-templated
metanephric nephron tubule formation
GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated
heart development
regulation of branching involved in lung morphogenesis
ureter urothelium development
branching involved in ureteric bud morphogenesis
cartilage development
Harderian gland development
positive regulation of kidney development
central nervous system development
heart valve formation
positive regulation of cartilage development
tissue homeostasis
metanephric tubule development
negative regulation of biomineral tissue development
endochondral bone morphogenesis
trachea cartilage development
male germ-line sex determination
lacrimal gland development
Notch signaling pathway
hair follicle development
Ćelijska diferencijacija
ureter development
regulation of cell cycle process
male gonad development
positive regulation of epithelial cell proliferation
cell fate specification
intestinal epithelial structure maintenance
positive regulation of extracellular matrix assembly
extracellular matrix organization
negative regulation of apoptotic process
GO:1901227 negative regulation of transcription by RNA polymerase II
Sertoli cell development
positive regulation of mesenchymal stem cell differentiation
retina development in camera-type eye
cellular response to interleukin-1
epithelial to mesenchymal transition
homeostasis of number of cells within a tissue
GO:0045996 negative regulation of transcription, DNA-templated
cAMP-mediated signaling
cartilage condensation
positive regulation of male gonad development
nucleosome assembly
negative regulation of bone mineralization
morphogenesis of a branching epithelium
neural crest cell development
protein kinase B signaling
somatic stem cell population maintenance
otic vesicle formation
otic vesicle development
endocardial cushion morphogenesis
cellular response to epidermal growth factor stimulus
positive regulation of epithelial cell differentiation
renal vesicle induction
GO:1901313 positive regulation of gene expression
regulation of epithelial cell proliferation involved in lung morphogenesis
regulation of cell population proliferation
heart valve morphogenesis
cytoskeleton organization
cochlea morphogenesis
positive regulation of cell population proliferation
epithelial cell proliferation involved in prostatic bud elongation
retinal rod cell differentiation
protein localization to nucleus
regulation of cell differentiation
positive regulation of phosphatidylinositol 3-kinase signaling
cellular response to heparin
negative regulation of epithelial cell differentiation
epithelial tube branching involved in lung morphogenesis
GO:0072468 Transdukcija signala
GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
negative regulation of pri-miRNA transcription by RNA polymerase II
chondrocyte differentiation
neural crest cell fate specification
cellular response to BMP stimulus
cell-cell adhesion
transcription initiation from RNA polymerase II promoter
GO:0034622 protein-containing complex assembly
anterior head development
morphogenesis of an epithelium
aortic valve morphogenesis
Regulacija ekspresije gena
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_000346

NM_011448

RefSeq (bjelančevina)

NP_000337

NP_035578

Lokacija (UCSC)Chr 17: 72.12 – 72.13 MbChr 11: 112.67 – 112.68 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Funkcija

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SOX-9 prepoznaje sekvencu CCTTGAG, zajedno sa ostalim članovima DNK-vezujućih proteina klase HMG-boksa. Ispoljava se proliferirajućim, ali ne hipertrofijskim hondrocitima, što je neophodno za diferencijaciju prekursorskih ćelija u hondrocite.[7] i, sa stereoidnim faktorom 1, regulira transkripciju gena antimelerovskog hormona antimüllerovakog hormona (AMH).[6]

SOX-9 također ima ključnu ulogu u spolnom razvoju muškaraca; radeći sa Sf1, SOX-9 može proizvesti AMH u Sertolijevim ćelijama da inhibira stvaranje ženskog reproduktivnog sistema.[8] Također komunicira s nekoliko drugih gena kako bi pospješio razvoj muških spolnih organa. Proces započinje kada faktor transkripcije testis-determinirajući faktor (kodiran iz regije za određivanje spola SRY Y hromosoma aktivira aktivnost SOX-9 vezivanjem za pojačivač uzvodne sekvence.[9] Nadalje, Sox9 aktivira FGF9 i formira povratne petlje sa FGF9[10] i PGD2.[9] Ove petlje su važne za proizvodnju SOX-9; bez njih, SOX-9-a bi ponestalo i gotovo sigurno bi uslijedio razvoj ženke. Aktivacija FGF9 puem SOX-9 pokreće vitalne procese u razvoju muškarca, poput stvaranja testisnih vrpci i umnožavanja Sertolijevih ćelija.[11] U razvoju mozga, njegov mišji ortolog Sox-9 inducira ekspresiju Wwp1, Wwp2 i miR-140 za regulaciju ulaska u korteksne ploče novorođenih nervnih ćelija i reguliranje grananja i stvaranje aksona u korteksnim neuronima.[12]

Klinički značaj

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Mutacije dovode do sindroma koštane malformacije zvane kampomelna displazija, često sa autosomnom reverzijom spola [6] i rascijepljeno nepce.[13]

Kod ljudi, SOX9 nalazi se u „genskoj pustinji“, na poziciji 17q24. Delecije, prekidi pomoću translokacije prelomnih tačaka i jednotočkastim mutacijaama visoko konzerviranih nekodirajućih elemenata lociranih > 1 Mb iz jedinice transkripcije s obje strane SOX9, povezane su sa Pierre-Robinovom sekvencom, često sa rascjepom nepca.[13][14]

Protein Sox9 sudjelovao je u pokretanju i napredovanju više solidnih tumora. funkcije Sox9 u [15] Njegova uloga kao glavnog regulatora morfogeneze tokom razvoja čovjeka čini ga idealnim kandidatom za perturbaciju u malignim tkivima. Konkretno, čini se da Sox9 izaziva invazivnost i otpornost na terapiju kod rakova prostati[16] kolorektuma,[17]dojkama[18] i drugim kancerina, a ponekad promovira i letalne metastaze.[19] Izleda da mnogi od ovih onkogenih efekata Sox9 ovise od doze.[20]

Kokalizacija i dinamika SOX9-a

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SOX9 je uglavnom lokaliziran u jedru i vrlo je mobilan. Studije na ćelijskoj liniji hondrocita otkrile su da je gotovo 50% SOX9-a vezano za DNK i izravno je reguliran vanjskim faktorima. Njegovo poluvrijeme boravka na DNK je ~ 14 sekundi.[21]

Uloga u reverziji spola

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Mutacije u Sox9 ili bilo koji pridruženi geni mogu izazvatireverziju pola i hermafroditizam (ili intersekse kod ljudi). Ako Fgf9, koji aktivira Sox9, nije prisutan, fetus s X i Y hromosomom može razviti ženske spolne žlijezde; isto vrijedi i ako nije prisutan Dax1.[11] Srodni fenomeni hermafroditizma mogu biti uzrokovani neobičnom aktivnošću SRY, obično kada se translocira na X-hromosom i njegova aktivnost pokrene se samo u nekim ćelijama.[22]

Interakcije

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Dokazano je da SOX9 ima interakcije sa steroidogenim faktorom 1,[8] MED12.[23] and MAF.[24]

Također pogledajte

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Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000125398 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000567 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Tommerup N, Schempp W, Meinecke P, Pedersen S, Bolund L, Brandt C, et al. (juni 1993). "Assignment of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17q24.3-q25.1". Nature Genetics. 4 (2): 170–4. doi:10.1038/ng0693-170. PMID 8348155.
  6. ^ a b c "Entrez Gene: SOX9 SRY (sex determining region Y)-box 9 (campomelic dysplasia, autosomal sex-reversal)".
  7. ^ Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (2015). Robbins and Cotran pathologic basis of disease (Ninth izd.). str. 1182. ISBN 9780808924500.
  8. ^ a b De Santa Barbara P, Bonneaud N, Boizet B, Desclozeaux M, Moniot B, Sudbeck P, et al. (novembar 1998). "Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Müllerian hormone gene". Molecular and Cellular Biology. 18 (11): 6653–65. doi:10.1128/mcb.18.11.6653. PMC 109250. PMID 9774680.
  9. ^ a b Moniot B, Declosmenil F, Barrionuevo F, Scherer G, Aritake K, Malki S, et al. (juni 2009). "The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation". Development. 136 (11): 1813–21. doi:10.1242/dev.032631. PMC 4075598. PMID 19429785.
  10. ^ Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, Chaboissier MC, et al. (juni 2006). "Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination". PLOS Biology. 4 (6): e187. doi:10.1371/journal.pbio.0040187. PMC 1463023. PMID 16700629.
  11. ^ a b Bouma GJ, Albrecht KH, Washburn LL, Recknagel AK, Churchill GA, Eicher EM (juli 2005). "Gonadal sex reversal in mutant Dax1 XY mice: a failure to upregulate Sox9 in pre-Sertoli cells". Development. 132 (13): 3045–54. doi:10.1242/dev.01890. PMID 15944188.
  12. ^ Ambrozkiewicz MC, Schwark M, Kishimoto-Suga M, Borisova E, Hori K, Salazar-Lázaro A, et al. (decembar 2018). "Polarity Acquisition in Cortical Neurons Is Driven by Synergistic Action of Sox9-Regulated Wwp1 and Wwp2 E3 Ubiquitin Ligases and Intronic miR-140". Neuron. 100 (5): 1097–1115.e15. doi:10.1016/j.neuron.2018.10.008. PMID 30392800.
  13. ^ a b Dixon MJ, Marazita ML, Beaty TH, Murray JC (mart 2011). "Cleft lip and palate: understanding genetic and environmental influences". Nature Reviews. Genetics. 12 (3): 167–78. doi:10.1038/nrg2933. PMC 3086810. PMID 21331089.
  14. ^ Benko S, Fantes JA, Amiel J, Kleinjan DJ, Thomas S, Ramsay J, et al. (mart 2009). "Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence". Nature Genetics. 41 (3): 359–64. doi:10.1038/ng.329. PMID 19234473.
  15. ^ Jo, A; Denduluri, S; Zhang, B; Wang, Z; Yin, L; Yan, Z; Kang, R; Shi, LL; Mok, J; Lee, MJ; Haydon, RC (decembar 2014). "The versatile functions of Sox9 in development, stem cells, and human diseases". Genes & Diseases. 1 (2): 149–161. doi:10.1016/j.gendis.2014.09.004. PMC 4326072. PMID 25685828.
  16. ^ Nouri, M; Massah, S; Caradec, J; Lubik, AA; Li, N; Truong, S; Lee, AR; Fazli, L; Ramnarine, VR; Lovnicki, JM; Moore, J; Wang, M; Foo, J; Gleave, ME; Hollier, BG; Nelson, C; Collins, C; Dong, X; Buttyan, R (9. 1. 2020). "Transient Sox9 Expression Facilitates Resistance to Androgen-Targeted Therapy in Prostate Cancer". Clinical Cancer Research. 26 (7): 1678–1689. doi:10.1158/1078-0432.CCR-19-0098. PMID 31919137.
  17. ^ Prévostel, C; Blache, P (novembar 2017). "The dose-dependent effect of SOX9 and its incidence in colorectal cancer". European Journal of Cancer. 86: 150–157. doi:10.1016/j.ejca.2017.08.037. PMID 28988015.
  18. ^ Grimm, D; Bauer, J; Wise, P; Krüger, M; Simonsen, U; Wehland, M; Infanger, M; Corydon, TJ (23. 3. 2019). "The role of SOX family members in solid tumours and metastasis". Seminars in Cancer Biology. doi:10.1016/j.semcancer.2019.03.004. PMID 30914279.
  19. ^ Aguilar-Medina, M; Avendaño-Félix, M; Lizárraga-Verdugo, E; Bermúdez, M; Romero-Quintana, JG; Ramos-Payan, R; Ruíz-García, E; López-Camarillo, C (2019). "SOX9 Stem-Cell Factor: Clinical and Functional Relevance in Cancer". Journal of Oncology. 2019: 6754040. doi:10.1155/2019/6754040. PMC 6463569. PMID 31057614.
  20. ^ Yang, X; Liang, R; Liu, C; Liu, JA; Cheung, MPL; Liu, X; Man, OY; Guan, XY; Lung, HL; Cheung, M (14. 1. 2019). "SOX9 is a dose-dependent metastatic fate determinant in melanoma". Journal of Experimental & Clinical Cancer Research : CR. 38 (1): 17. doi:10.1186/s13046-018-0998-6. PMC 6330758. PMID 30642390.
  21. ^ Govindaraj K, Hendriks J, Lidke DS, Karperien M, Post JN (januar 2019). "Changes in Fluorescence Recovery After Photobleaching (FRAP) as an indicator of SOX9 transcription factor activity". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1862 (1): 107–117. doi:10.1016/j.bbagrm.2018.11.001. PMID 30465885.
  22. ^ Margarit E, Coll MD, Oliva R, Gómez D, Soler A, Ballesta F (januar 2000). "SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite". American Journal of Medical Genetics. 90 (1): 25–8. doi:10.1002/(SICI)1096-8628(20000103)90:1<25::AID-AJMG5>3.0.CO;2-5. PMID 10602113.
  23. ^ Zhou R, Bonneaud N, Yuan CX, de Santa Barbara P, Boizet B, Schomber T, et al. (juli 2002). "SOX9 interacts with a component of the human thyroid hormone receptor-associated protein complex". Nucleic Acids Research. 30 (14): 3245–52. doi:10.1093/nar/gkf443. PMC 135763. PMID 12136106.
  24. ^ Huang W, Lu N, Eberspaecher H, De Crombrugghe B (decembar 2002). "A new long form of c-Maf cooperates with Sox9 to activate the type II collagen gene". The Journal of Biological Chemistry. 277 (52): 50668–75. doi:10.1074/jbc.M206544200. PMID 12381733.

Dopunska literatura

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Vanjski linkovi

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SOX9 detalji ljudskog genoma u UCSC Genome Browser.