Wikipedia

TBX3

T-boksni transkripcijski faktor TBX3 jest protein koji je kod ljudi kodiran genom TBX3.[5][6]

TBX3
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1H6F

Identifikatori
AliasiTBX3
Vanjski ID-jeviOMIM: 601621 MGI: 98495 HomoloGene: 4371 GeneCards: TBX3
Lokacija gena (čovjek)
Hromosom 12 (čovjek)
Hrom.Hromosom 12 (čovjek)[1]
Hromosom 12 (čovjek)
Genomska lokacija za TBX3
Genomska lokacija za TBX3
Bend12q24.21Početak114,670,255 bp[1]
Kraj114,684,175 bp[1]
Lokacija gena (miš)
Hromosom 5 (miš)
Hrom.Hromosom 5 (miš)[2]
Hromosom 5 (miš)
Genomska lokacija za TBX3
Genomska lokacija za TBX3
Bend5 F|5 60.34 cMPočetak119,808,734 bp[2]
Kraj119,822,789 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific
• sequence-specific DNA binding
• GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding
• GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity
• vezivanje sa DNK
• GO:0001948, GO:0016582 vezivanje za proteine
• GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific
Ćelijska komponenta• jedro
Biološki proces• forelimb morphogenesis
• Ćelijsko starenje
• branching involved in mammary gland duct morphogenesis
• positive regulation of stem cell proliferation
• atrioventricular bundle cell differentiation
• negative regulation of epithelial cell differentiation
• female genitalia development
• transcription, DNA-templated
• male genitalia development
• multicellular organism development
• anterior/posterior axis specification, embryo
• outflow tract morphogenesis
• skeletal system development
• ventricular septum morphogenesis
• embryonic forelimb morphogenesis
• cardiac muscle cell fate commitment
• 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
• heart morphogenesis
• regulation of cell population proliferation
• heart looping
• negative regulation of myoblast differentiation
• specification of animal organ position
• stem cell population maintenance
• luteinizing hormone secretion
• follicle-stimulating hormone secretion
• blood vessel development
• positive regulation of cell population proliferation
• GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated
• roof of mouth development
• mammary placode formation
• in utero embryonic development
• mesoderm morphogenesis
• GO:0009373 regulation of transcription, DNA-templated
• limb morphogenesis
• sinoatrial node cell development
• positive regulation of cell cycle
• cardiac muscle cell differentiation
• limbic system development
• embryonic hindlimb morphogenesis
• animal organ morphogenesis
• embryonic heart tube development
• embryonic digit morphogenesis
• mammary gland development
• GO:1901227 negative regulation of transcription by RNA polymerase II
• GO:0045996 negative regulation of transcription, DNA-templated
• negative regulation of apoptotic process
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

6926

21386

Ensembl

ENSG00000135111

ENSMUSG00000018604

UniProt

O15119

P70324

RefSeq (mRNK)

NM_016569
NM_005996

NM_011535
NM_198052

RefSeq (bjelančevina)

NP_005987
NP_057653

NP_035665
NP_932169

Lokacija (UCSC)Chr 12: 114.67 – 114.68 MbChr 5: 119.81 – 119.82 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

T-boks 3 (TBX3) je član porodice gena T-kutije transkripcijskih faktora koji svi dijele visoko konzervirani domen vezanja za DNK poznat kao T-kutija. Porodica gena ove kutije sastoji se od 17 članova kod miševa i ljudi, koji su grupirani u pet potporodica, i to Brachyury (T), T-moždana (Tbr1), TBX1, TBX2 i TBX6. Tbx3 je član potporodice Tbx2 koja uključuje Tbx2, Tbx4 i Tbx5.[7] Ljudski gen TBX3 nalazi se u hromosomu 12, na poziciji 12q23-24.1 i sastoji se od sedam egzon koji kodiraju protein od 723 aminokiseline (prema ENSEMBL, sklop GRCh38.p12).

Prerada transkripta

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Alternativna prerada trankripta rezultira u najmanje četiri različita TBX3 izoforme s TBX3 i TBX3+2a kao dominantnim izoformama. TBX3 +2a je rezultat alternativne prerade drugog introna, što dovodi do dodavanja +2a egzona, pa prema tome ova izoforma ima dodatnih 20 aminokiselina unutar domena vezanja T-kutije DNK.[8][9] Funkcije TBX3 i TBX3+2a mogu se malo razlikovati kod različitih tipova ćelija.[9][10][11][12][13][14]

Aminokiselinska sekvenca

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Dužina polipeptidnog lanca je 743 aminokiseline, a molekulska težina 79.389 Da.[15]

1020304050
MSLSMRDPVIPGTSMAYHPFLPHRAPDFAMSAVLGHQPPFFPALTLPPNG
AAALSLPGALAKPIMDQLVGAAETGIPFSSLGPQAHLRPLKTMEPEEEVE
DDPKVHLEAKELWDQFHKRGTEMVITKSGRRMFPPFKVRCSGLDKKAKYI
LLMDIIAADDCRYKFHNSRWMVAGKADPEMPKRMYIHPDSPATGEQWMSK
VVTFHKLKLTNNISDKHGFTLAFPSDHATWQGNYSFGTQTILNSMHKYQP
RFHIVRANDILKLPYSTFRTYLFPETEFIAVTAYQNDKITQLKIDNNPFA
KGFRDTGNGRREKRKQLTLQSMRVFDERHKKENGTSDESSSEQAAFNCFA
QASSPAASTVGTSNLKDLCPSEGESDAEAESKEEHGPEACDAAKISTTTS
EEPCRDKGSPAVKAHLFAAERPRDSGRLDKASPDSRHSPATISSSTRGLG
AEERRSPVREGTAPAKVEEARALPGKEAFAPLTVQTDAAAAHLAQGPLPG
LGFAPGLAGQQFFNGHPLFLHPSQFAMGGAFSSMAAAGMGPLLATVSGAS
TGVSGLDSTAMASAAAAQGLSGASAATLPFHLQQHVLASQGLAMSPFGSL
FPYPYTYMAAAAAASSAAASSSVHRHPFLNLNTMRPRLRYSPYSIPVPVP
DGSSLLTTALPSMAAAAGPLDGKVAALAASPASVAVDSGSELNSRSSTLS
SSSMSLSPKLCAEKEAATSELQSIQRLVSGLEAKPDRSRSASP
Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Struktura i funkcija

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TBX3 ima domene koji su važni za njegovu funkciju transkripcijskog faktora, a koje uključuju domen koja se veže za DNK (DBD), zvami i T-box, signal nuklearne lokalizacije, dva domena represije (R2 i R1) i aktivacijsko područje (A).[16] T-okvir prepoznaje palindromsku DNK-sekvencu (T (G/C) ACACCT AGGTGTGAAATT) poznatu kao T-element, ili pola mjesta unutar ove sekvence koja se naziva pola T-elemenata, iako može prepoznati i varijacije unutar konsenzusnih sekvenci T-elemenata. Iako postoji 29 predviđenih mjesta fosforilacija u proteinu TBX3, samo su SP190, SP692 i S720 u potpunosti okarakterizirani. Uključene kinaze su ciklin A-CDK2 na SP190 ili SP354, p38 mitogen-aktivirani protein (MAP) kinaza na SP692 u embrionskim ćelijama bubrega i AKT3 na S720 kod melanoma. Ove izmjene djeluju na konteksto zavisan način i promiču stabilnost proteina TBX3, jedarnu lokalizaciju i transkripcijsku aktivnost.[17][18]

TBX3 može aktivirati i/ili potisnuti svoje ciljne gene vezivanjem T-elementa ili polovine T-elemenata.[19] Zaista, Tbx3 veže visoko konzervirane T-elemente za aktiviranje promotora Eomes, T, Sox17 i Gata6, koji su bitni faktori za diferencijaciju mezoderma i vanembrionskog endoderma.[20][21] Nadalje, u kontekstu raka, TBX3 direktno potiskuje regulatore ćelijskog ciklusa p19ARF/p14ARF,[22] p21WAF1 [23] i TBX2 [24] kao i E-kadherin, koji kodira ćelijsku adhezijsku molekulu, za podstcanje proliferacije i migracije. TBX3 izravno potiskuje područje promotora PTEN kojem nedostaju navodni T-elementi, ali koji čini važnu regulatornu jedinicu za PTEN-ove transkripcijske aktivatore, čime se povećava mogućnost da TBX3 može također potisnuti neke svoje ciljne gene ometajući transkripcijske aktivatore.[25]

Funkcija TBX3 ili kao transkripcijskog represora ili transkripcijskog aktivatora, djelimično je modulirana proteinskim kofaktorima. Naprimjer, može stupiti u interakciju s drugim faktorima transkripcije, poput Nkx2-5, Msx 1/2[26] i Sox4[27] to assist it binding to its target genes to regulate heart development [10][28][29][30][31] i može stupiti u interakciju s histon-deacetilazima (HDACs) 1, 2, 3 i 5, kako bi potisnuo p14ARF u karcinomu dojke i s HDAC5, kako bi supresirao E-kadherin za podsticanje metastaza u hepatoćelijskom karcinomu.[32][33] Na kraju, TBX3 može također surađivati s drugim faktorima kako bi inhibirao proces prerade iRNK direktnim vezanjem RNK koje sadrže jezgro motiva T-elementa. Zaista, TBX3 stupa u interakciju s koaktivatorom AP1 i receptorom estrogena (CAPERα), kako bi potisnuo dugolančanu nekodirajuću RNK, urotelijski karcinom povezan 1 (UCA1), koji dovodi do zaobilaženja starenja, stabilizacijom p16INK4a iRNK.[34]

Klinički značaj

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TBX3 je uključen u ljudske bolesti, uključujući sindrom ulnusne dojke,[35] gojaznost,[36] reumatoidni artritis[37] i kancer.[38]

Kod ljudi, heterozigotne mutacije TBX3 dovode do autosomno dominantnog razvojnog poremećaja, sindroma ulnusne dojke (UMS), koji se odlikuje nizom kliničkih značajki,uključujući hipoplaziju mliječnih i apokrinih žlijezda, defekte gornjih udova, malformacije areola, zubne strukture, srca i genitalija.[8][39] Prijavljeno je nekoliko UMS-a koji uzrokuju mutacije u TBX3 genu, uključujući pet nonsens mutacija, osam pomaka okvira (zbog delecija, duplikacija i insercija), tri misens mutacije i dvije mutacije na mjestu prerade. Misens mutacije unutar T-domen ili gubitak RD1 rezultiraju aberantnim transkriptima i krnjim proteinima TBX3. Ove mutacije dovode do smanjenja vezivanja DNK, kontrole transkripcije i regulacije prerade TBX3 i gubitka funkcije, a povezane su s najtežim fenotipom UMS-a.[22][40][41][42]

Tbx3 je eksprimiran u heterogenim populacijama neurona jezgara hipotalamusnog luka, koja kontroliraju energetsku homeostazu, regulirajući apetit i potrošnju energije, a pokazalo se da ablacija funkcije TBX3 u tim neuronima uzrokuje pretilost na modelima miša. Važno je napomenuti da se pokazalo da je Tbx3 ključni faktor u pokretanju funkcionalne heterogenosti hipotalamusnih neurona, a ta je funkcija konzervirana kod miševa, drozofila i ljudi, za osjetljivost na reumatoidni artritis (RA), a nedavno je istraživanje identificiralo Tbx3 kao gen kandidat za RA u mišjim modelima izazvanim kolagenom artritisom (CIA).[37][43] Ozbiljnost RA direktno je povezana sa serumskim nivoima TBX3 u modelima CIA miša. Nadalje, pokazalo se da Tbx3 potiskuje proliferaciju B-limfocita i aktivira humoralni imunski odgovor, koji je povezan s hroničnom upalom sinovijalnih žlijezda, što dovodi do RA. Tbx3 bi stoga mogao biti važan faktor u regulaciji imunskog sistema i mogao bi se koristiti kao biomarker za dijagnozu ozbiljnosti RA.

TBX3 je prekomjerno izražen u širokom rasponu karcinoma (karcinom dojke, gušterače, melanom, rak jetre, pluća, želuca, jajnika, mjehura i glave i vrata) i sarkoma (hondrosarkom, fibrosarkom, liposarkom, rabdomiosarkom i sinovijalni sarkom) te doprinosi nekoliko obilježja raka. Zaista, TBX3 može zaobići ćelijsko starenje, apoptozu i anoikis, kao i podsticati nekontroliranu proliferaciju ćelija, stvaranje tumora, angiogenezu i metastaze.[44][45][46] Nadalje, TBX3 doprinosi širenju matičnih ćelija raka (CSC) i ključni je faktor u regulaciji gena povezanih pluripotencijom u tim ćelijama. CSC doprinosi recidivu tumora i gubitak otpornosti , pa ovo može biti još jedan mehanizam pomoću TBX3 doprinosi stvaranju raka i agresivnosti tumora.[47] Mehanizmi pomoću kojih TBX3 doprinosi onkogenim procesima djelimično uključuju njegovu sposobnost da inhibira puteve supresije tumora p14ARF/p53/p21WAF1/CIP1,[32][48] p16INK4a/pRb, p57KIP2,[49] PTEN,[25] E-cadherin[44][45] and activating the angiogenesis-associated genes FGF2 and VEGF-A[50] i EMT gena SNAI.

Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000135111 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000018604 - 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. ^ Li QY, Newbury-Ecob RA, Terrett JA, Wilson DI, Curtis AR, Yi CH, Gebuhr T, Bullen PJ, Robson SC, Strachan T, Bonnet D, Lyonnet S, Young ID, Raeburn JA, Buckler AJ, Law DJ, Brook JD (Jan 1997). "Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family". Nature Genetics. 15 (1): 21–9. doi:10.1038/ng0197-21. PMID 8988164. S2CID 22619598.
  6. ^ "Entrez Gene: TBX3 T-box 3 (ulnar mammary syndrome)".
  7. ^ Papaioannou VE (oktobar 2014). "The T-box gene family: emerging roles in development, stem cells and cancer". Development. 141 (20): 3819–33. doi:10.1242/dev.104471. PMC 4197708. PMID 25294936.
  8. ^ a b Bamshad M, Lin RC, Law DJ, Watkins WC, Krakowiak PA, Moore ME, et al. (juli 1997). "Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome". Nature Genetics. 16 (3): 311–5. doi:10.1038/ng0797-311. PMID 9207801. S2CID 2415047.
  9. ^ a b Fan W, Huang X, Chen C, Gray J, Huang T (august 2004). "TBX3 and its isoform TBX3+2a are functionally distinctive in inhibition of senescence and are overexpressed in a subset of breast cancer cell lines". Cancer Research. 64 (15): 5132–9. doi:10.1158/0008-5472.CAN-04-0615. PMID 15289316. S2CID 40051568.
  10. ^ a b Hoogaars WM, Barnett P, Rodriguez M, Clout DE, Moorman AF, Goding CR, Christoffels VM (juni 2008). "TBX3 and its splice variant TBX3 + exon 2a are functionally similar". Pigment Cell & Melanoma Research. 21 (3): 379–87. doi:10.1111/j.1755-148X.2008.00461.x. PMID 18444963. S2CID 26106714.
  11. ^ Rodriguez M, Aladowicz E, Lanfrancone L, Goding CR (oktobar 2008). "Tbx3 represses E-cadherin expression and enhances melanoma invasiveness". Cancer Research. 68 (19): 7872–81. doi:10.1158/0008-5472.CAN-08-0301. PMID 18829543.
  12. ^ Zhao D, Wu Y, Chen K (februar 2014). "Tbx3 isoforms are involved in pluripotency maintaining through distinct regulation of Nanog transcriptional activity". Biochemical and Biophysical Research Communications. 444 (3): 411–4. doi:10.1016/j.bbrc.2014.01.093. PMID 24472544.
  13. ^ Krstic M, Macmillan CD, Leong HS, Clifford AG, Souter LH, Dales DW, et al. (august 2016). "The transcriptional regulator TBX3 promotes progression from non-invasive to invasive breast cancer". BMC Cancer. 16 (1): 671. doi:10.1186/s12885-016-2697-z. PMC 4994202. PMID 27553211.
  14. ^ Krstic M, Kolendowski B, Cecchini MJ, Postenka CO, Hassan HM, Andrews J, et al. (juni 2019). "TBX3 promotes progression of pre-invasive breast cancer cells by inducing EMT and directly up-regulating SLUG". The Journal of Pathology. 248 (2): 191–203. doi:10.1002/path.5245. PMC 6593675. PMID 30697731.
  15. ^ "UniProt, O15119". Pristupljeno 14. 8. 2021.
  16. ^ Carlson H, Ota S, Song Y, Chen Y, Hurlin PJ (maj 2002). "Tbx3 impinges on the p53 pathway to suppress apoptosis, facilitate cell transformation and block myogenic differentiation". Oncogene. 21 (24): 3827–35. doi:10.1038/sj.onc.1205476. PMID 12032820.
  17. ^ Willmer T, Peres J, Mowla S, Abrahams A, Prince S (2. 10. 2015). "The T-Box factor TBX3 is important in S-phase and is regulated by c-Myc and cyclin A-CDK2". Cell Cycle. 14 (19): 3173–83. doi:10.1080/15384101.2015.1080398. PMC 4825571. PMID 26266831.
  18. ^ Yano T, Yamazaki Y, Adachi M, Okawa K, Fort P, Uji M, et al. (april 2011). "Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling". The Journal of Cell Biology. 193 (2): 319–32. doi:10.1083/jcb.201009100. PMC 3080255. PMID 21482718.
  19. ^ Wilson V, Conlon FL (2002). "The T-box family". Genome Biology. 3 (6): REVIEWS3008. doi:10.1186/gb-2002-3-6-reviews3008. PMC 139375. PMID 12093383.
  20. ^ Weidgang CE, Russell R, Tata PR, Kühl SJ, Illing A, Müller M, et al. (septembar 2013). "TBX3 Directs Cell-Fate Decision toward Mesendoderm". Stem Cell Reports. 1 (3): 248–65. doi:10.1016/j.stemcr.2013.08.002. PMC 3849240. PMID 24319661.
  21. ^ Lu R, Yang A, Jin Y (mart 2011). "Dual functions of T-box 3 (Tbx3) in the control of self-renewal and extraembryonic endoderm differentiation in mouse embryonic stem cells". The Journal of Biological Chemistry. 286 (10): 8425–36. doi:10.1074/jbc.M110.202150. PMC 3048727. PMID 21189255.
  22. ^ a b Lingbeek ME, Jacobs JJ, van Lohuizen M (juli 2002). "The T-box repressors TBX2 and TBX3 specifically regulate the tumor suppressor gene p14ARF via a variant T-site in the initiator". The Journal of Biological Chemistry. 277 (29): 26120–7. doi:10.1074/jbc.M200403200. PMID 12000749.
  23. ^ Willmer T, Hare S, Peres J, Prince S (mart 2016). "The T-box transcription factor TBX3 drives proliferation by direct repression of the p21(WAF1) cyclin-dependent kinase inhibitor". Cell Division. 11 (1): 6. doi:10.1186/s13008-016-0019-0. PMC 4840944. PMID 27110270.
  24. ^ Li J, Ballim D, Rodriguez M, Cui R, Goding CR, Teng H, Prince S (decembar 2014). "The anti-proliferative function of the TGF-β1 signaling pathway involves the repression of the oncogenic TBX2 by its homologue TBX3". The Journal of Biological Chemistry. 289 (51): 35633–43. doi:10.1074/jbc.M114.596411. PMC 4271245. PMID 25371204.
  25. ^ a b Burgucu D, Guney K, Sahinturk D, Ozbudak IH, Ozel D, Ozbilim G, Yavuzer U (oktobar 2012). "Tbx3 represses PTEN and is over-expressed in head and neck squamous cell carcinoma". BMC Cancer. 12 (1): 481. doi:10.1186/1471-2407-12-481. PMC 3517435. PMID 23082988.
  26. ^ Boogerd KJ, Wong LY, Christoffels VM, Klarenbeek M, Ruijter JM, Moorman AF, Barnett P (juni 2008). "Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43". Cardiovascular Research. 78 (3): 485–93. doi:10.1093/cvr/cvn049. PMID 18285513.
  27. ^ Boogerd CJ, Wong LY, van den Boogaard M, Bakker ML, Tessadori F, Bakkers J, et al. (decembar 2011). "Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43". Cellular and Molecular Life Sciences. 68 (23): 3949–61. doi:10.1007/s00018-011-0693-7. PMC 3214269. PMID 21538160.
  28. ^ Bakker ML, Boukens BJ, Mommersteeg MT, Brons JF, Wakker V, Moorman AF, Christoffels VM (juni 2008). "Transcription factor Tbx3 is required for the specification of the atrioventricular conduction system". Circulation Research. 102 (11): 1340–9. doi:10.1161/circresaha.107.169565. PMID 18467625.
  29. ^ Christoffels VM, Habets PE, Franco D, Campione M, de Jong F, Lamers WH, et al. (juli 2000). "Chamber formation and morphogenesis in the developing mammalian heart". Developmental Biology. 223 (2): 266–78. doi:10.1006/dbio.2000.9859. PMID 10882515.
  30. ^ Christoffels VM, Hoogaars WM, Tessari A, Clout DE, Moorman AF, Campione M (april 2004). "T-box transcription factor Tbx2 represses differentiation and formation of the cardiac chambers". Developmental Dynamics. 229 (4): 763–70. doi:10.1002/dvdy.10487. PMID 15042700. S2CID 29623563.
  31. ^ Stennard FA, Harvey RP (novembar 2005). "T-box transcription factors and their roles in regulatory hierarchies in the developing heart". Development. 132 (22): 4897–910. doi:10.1242/dev.02099. PMID 16258075.
  32. ^ a b Yarosh W, Barrientos T, Esmailpour T, Lin L, Carpenter PM, Osann K, et al. (februar 2008). "TBX3 is overexpressed in breast cancer and represses p14 ARF by interacting with histone deacetylases". Cancer Research. 68 (3): 693–9. doi:10.1158/0008-5472.can-07-5012. PMID 18245468.
  33. ^ Dong L, Lyu X, Faleti OD, He ML (septembar 2018). "The special stemness functions of Tbx3 in stem cells and cancer development". Seminars in Cancer Biology. 57: 105–110. doi:10.1016/j.semcancer.2018.09.010. PMID 30268432.
  34. ^ Kumar PP, Emechebe U, Smith R, Franklin S, Moore B, Yandell M, et al. (maj 2014). "Coordinated control of senescence by lncRNA and a novel T-box3 co-repressor complex". eLife. 3. doi:10.7554/elife.02805. PMC 4071561. PMID 24876127.
  35. ^ Frank DU, Emechebe U, Thomas KR, Moon AM (2. 7. 2013). Dettman R (ured.). "Mouse TBX3 mutants suggest novel molecular mechanisms for Ulnar-mammary syndrome". PLOS ONE. 8 (7): e67841. Bibcode:2013PLoSO...867841F. doi:10.1371/journal.pone.0067841. PMC 3699485. PMID 23844108.
  36. ^ Greška kod citiranja: Nevaljana oznaka <ref>; nije naveden tekst za reference s imenom Quarta 222–235
  37. ^ a b Sardar S, Kerr A, Vaartjes D, Moltved ER, Karosiene E, Gupta R, Andersson Å (januar 2019). "The oncoprotein TBX3 is controlling severity in experimental arthritis". Arthritis Research & Therapy. 21 (1): 16. doi:10.1186/s13075-018-1797-3. PMC 6329118. PMID 30630509.
  38. ^ Willmer T, Cooper A, Peres J, Omar R, Prince S (juli 2017). "The T-Box transcription factor 3 in development and cancer". Bioscience Trends. 11 (3): 254–266. doi:10.5582/bst.2017.01043. PMID 28579578.
  39. ^ Linden H, Williams R, King J, Blair E, Kini U (decembar 2009). "Ulnar Mammary syndrome and TBX3: expanding the phenotype". American Journal of Medical Genetics. Part A. 149A (12): 2809–12. doi:10.1002/ajmg.a.33096. PMID 19938096. S2CID 409905.
  40. ^ Meneghini V, Odent S, Platonova N, Egeo A, Merlo GR (mart 2006). "Novel TBX3 mutation data in families with ulnar-mammary syndrome indicate a genotype-phenotype relationship: mutations that do not disrupt the T-domain are associated with less severe limb defects". European Journal of Medical Genetics. 49 (2): 151–8. doi:10.1016/j.ejmg.2005.04.021. PMID 16530712.
  41. ^ Carlson H, Ota S, Campbell CE, Hurlin PJ (oktobar 2001). "A dominant repression domain in Tbx3 mediates transcriptional repression and cell immortalization: relevance to mutations in Tbx3 that cause ulnar-mammary syndrome". Human Molecular Genetics. 10 (21): 2403–13. doi:10.1093/hmg/10.21.2403. PMID 11689487.
  42. ^ Kumar PP, Franklin S, Emechebe U, Hu H, Moore B, Lehman C, Yandell M, Moon AM (mart 2014). "TBX3 regulates splicing in vivo: a novel molecular mechanism for Ulnar-mammary syndrome". PLOS Genetics. 10 (3): e1004247. doi:10.1371/journal.pgen.1004247. OCLC 908304248. PMC 3967948. PMID 24675841.
  43. ^ Julià A, Ballina J, Cañete JD, Balsa A, Tornero-Molina J, Naranjo A, et al. (august 2008). "Genome-wide association study of rheumatoid arthritis in the Spanish population: KLF12 as a risk locus for rheumatoid arthritis susceptibility". Arthritis and Rheumatism. 58 (8): 2275–86. doi:10.1002/art.23623. PMID 18668548.
  44. ^ a b Feng X, Yao W, Zhang Z, Yuan F, Liang L, Zhou J, et al. (juli 2018). "T-box Transcription Factor Tbx3 Contributes to Human Hepatocellular Carcinoma Cell Migration and Invasion by Repressing E-Cadherin Expression". Oncology Research. 26 (6): 959–966. doi:10.3727/096504017x15145624664031. PMC 7844722. PMID 29295731.
  45. ^ a b Dong L, Dong Q, Chen Y, Li Y, Zhang B, Zhou F, et al. (24. 8. 2018). "Novel HDAC5-interacting motifs of Tbx3 are essential for the suppression of E-cadherin expression and for the promotion of metastasis in hepatocellular carcinoma". Signal Transduction and Targeted Therapy. 3 (1): 22. doi:10.1038/s41392-018-0025-6. PMC 6107554. PMID 30151243.
  46. ^ Wang Y (april 2018). "TBX3 gene in renal carcinoma and its clinical significance". Oncology Letters. 15 (4): 4235–4240. doi:10.3892/ol.2018.7841. PMC 5835868. PMID 29541189.
  47. ^ Jones PA, Baylin SB (juni 2002). "The fundamental role of epigenetic events in cancer". Nature Reviews. Genetics. 3 (6): 415–28. doi:10.1038/nrg816. PMID 12042769. S2CID 2122000.
  48. ^ Brummelkamp TR, Kortlever RM, Lingbeek M, Trettel F, MacDonald ME, van Lohuizen M, Bernards R (februar 2002). "TBX-3, the gene mutated in Ulnar-Mammary Syndrome, is a negative regulator of p19ARF and inhibits senescence". The Journal of Biological Chemistry. 277 (8): 6567–72. doi:10.1074/jbc.m110492200. PMID 11748239.
  49. ^ Li X, Ruan X, Zhang P, Yu Y, Gao M, Yuan S, et al. (maj 2018). "KIP2 repression". Oncogene. 37 (21): 2773–2792. doi:10.1038/s41388-017-0090-2. PMID 29511350. S2CID 3706091.
  50. ^ Perkhofer L, Walter K, Costa IG, Carrasco MC, Eiseler T, Hafner S, et al. (septembar 2016). "Tbx3 fosters pancreatic cancer growth by increased angiogenesis and activin/nodal-dependent induction of stemness". Stem Cell Research. 17 (2): 367–378. doi:10.1016/j.scr.2016.08.007. PMID 27632063.

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