GATA3

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GATA3
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases GATA3, HDR, HDRS, GATA binding protein 3
External IDs MGI: 95663 HomoloGene: 1550 GeneCards: 2625
Genetically Related Diseases
Disease Name References
Rheumatoid Arthritis
acute lymphoblastic leukemia
Hodgkin's lymphoma
RNA expression pattern
PBB GE GATA3 209602 s at tn.png

PBB GE GATA3 209603 at tn.png

PBB GE GATA3 209604 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001002295
NM_002051

NM_008091

RefSeq (protein)

NP_001002295.1
NP_002042.1

NP_032117.1

Location (UCSC) Chr 10: 8.05 – 8.08 Mb Chr 2: 9.86 – 9.89 Mb
PubMed search [4] [5]
Wikidata
View/Edit Human View/Edit Mouse

Trans-acting T-cell-specific transcription factor GATA-3 is a protein that in humans is encoded by the GATA3 gene.[6][7][8]

Function[edit]

GATA-3 belongs to the GATA family of transcription factors. It regulates luminal epithelial cell differentiation in the mammary gland.[9] The protein contains two GATA-type zinc fingers and is an important regulator of T cell development and plays an important role in endothelial cell biology. GATA-3 has been shown to promote the secretion of IL-4, IL-5, and IL-13 from Th2 cells, and induces the differentiation of Th0 cells towards this Th2 cell subtype while suppressing their differentiation towards Th1 cells.[10] It is hypothesised that GATA-3 may play tissue-specific roles.[11] It has been suggested that GATA-3 is regulated in CD4+ T cells at a transcriptional level through the IL-4 receptor, as well as translationally through T cell receptor signaling. [12]

Clinical significance[edit]

Defects in this gene are the cause of hypoparathyroidism with sensorineural deafness and renal dysplasia.

Breast cancer[edit]

GATA-3 is one of the three genes mutated in >10% of breast cancers (Cancer Genome Atlas).[13]

GATA-3 was shown to be required for the luminal A type of breast cancer, intertwined in pathways with ERα[14][15] but also androgen receptor signaling in ER-/AR+ tumors.[16]

Nuclear expression of GATA-3 in breast cancer is considered a marker of luminal cancer in ER+ cancer and luminal androgen responsive cancer in ER-/AR+ tumors.[17] It is highly coexpressed with FOXA1 and serves as negative predictor of basal subtype and ERBB2 subtype.[16][18][19] GATA-3 was shown to directly regulate luminal cell differentiation in mouse models of breast cancer.[20] It is also considered a strong predictor of taxane and platin salts insensitivity.[citation needed]

Insulin has been shown in experimental models to downregulate expression of GATA3 by causing overexpression of T-bet, resulting in resistance to endocrine therapy.[21]

Interactions[edit]

GATA3 has been shown to interact with LMO1,[22][23] ER and FOXA1.[19]

See also[edit]

References[edit]

  1. ^ "chibi.ubc.ca/Gemma/phenotypes.html?phenotypeUrlId=DOID_7148&geneId=52152". 
  2. ^ "chibi.ubc.ca/Gemma/phenotypes.html?phenotypeUrlId=DOID_9952&geneId=52152". 
  3. ^ "chibi.ubc.ca/Gemma/phenotypes.html?phenotypeUrlId=DOID_8567&geneId=52152". 
  4. ^ "Human PubMed Reference:". 
  5. ^ "Mouse PubMed Reference:". 
  6. ^ Joulin V, Bories D, Eléouet JF, Labastie MC, Chrétien S, Mattéi MG, Roméo PH (Jul 1991). "A T-cell specific TCR delta DNA binding protein is a member of the human GATA family". The EMBO Journal. 10 (7): 1809–16. PMC 452855free to read. PMID 2050118. 
  7. ^ Yamashita M, Ukai-Tadenuma M, Miyamoto T, Sugaya K, Hosokawa H, Hasegawa A, Kimura M, Taniguchi M, DeGregori J, Nakayama T (Jun 2004). "Essential role of GATA3 for the maintenance of type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci". The Journal of Biological Chemistry. 279 (26): 26983–90. doi:10.1074/jbc.M403688200. PMID 15087456. 
  8. ^ "Entrez Gene: GATA3 GATA binding protein 3". 
  9. ^ Kouros-Mehr H, Slorach EM, Sternlicht MD, Werb Z (Dec 2006). "GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland". Cell. 127 (5): 1041–55. doi:10.1016/j.cell.2006.09.048. PMC 2646406free to read. PMID 17129787. 
  10. ^ Yagi R, Zhu J, Paul WE (Jul 2011). "An updated view on transcription factor GATA3-mediated regulation of Th1 and Th2 cell differentiation". International Immunology. 23 (7): 415–20. doi:10.1093/intimm/dxr029. PMID 21632975. 
  11. ^ Wilson BJ (2008). "Does GATA3 act in tissue-specific pathways? A meta-analysis-based approach". Journal of Carcinogenesis. 7: 6. doi:10.4103/1477-3163.43426. PMC 2669725free to read. PMID 19008565. 
  12. ^ Cook KD, Miller J (September 15, 2010). "TCR-dependent translational control of GATA-3 enhances Th2 differentiation". Journal of Immunology. 185 (6): 3209–3216. doi:10.4049/jimmunol.0902544. PMC 3993005free to read. PMID 20696860. 
  13. ^ Koboldt DC, Fulton RS, McLellan MD (Oct 2012). "Comprehensive molecular portraits of human breast tumours". Nature. 490 (7418): 61–70. doi:10.1038/nature11412. PMC 3465532free to read. PMID 23000897. 
  14. ^ Wilson BJ, Giguère V (2008). "Meta-analysis of human cancer microarrays reveals GATA3 is integral to the estrogen receptor alpha pathway". Molecular Cancer. 7: 49. doi:10.1186/1476-4598-7-49. PMC 2430971free to read. PMID 18533032. 
  15. ^ Dydensborg AB, Rose AA, Wilson BJ, Grote D, Paquet M, Giguère V, Siegel PM, Bouchard M (Jul 2009). "GATA3 inhibits breast cancer growth and pulmonary breast cancer metastasis". Oncogene. 28 (29): 2634–42. doi:10.1038/onc.2009.126. PMID 19483726. 
  16. ^ a b Sanga S, Broom BM, Cristini V, Edgerton ME (2009). "Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family". BMC Medical Genomics. 2: 59. doi:10.1186/1755-8794-2-59. PMC 2753593free to read. PMID 19747394. 
  17. ^ Kouros-Mehr H, Kim JW, Bechis SK, Werb Z (Apr 2008). "GATA-3 and the regulation of the mammary luminal cell fate". Current Opinion in Cell Biology. 20 (2): 164–70. doi:10.1016/j.ceb.2008.02.003. PMC 2397451free to read. PMID 18358709. 
  18. ^ Jacquemier J, Charafe-Jauffret E, Monville F, Esterni B, Extra JM, Houvenaeghel G, Xerri L, Bertucci F, Birnbaum D (2009). "Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer". Breast Cancer Research. 11 (2): R23. doi:10.1186/bcr2249. PMC 2688952free to read. PMID 19405945. 
  19. ^ a b Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, Costa S, Vieira D, Lopes N, Lam EW, Lunet N, Schmitt F (2009). "Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours". Breast Cancer Research. 11 (3): R40. doi:10.1186/bcr2327. PMC 2716509free to read. PMID 19549328. 
  20. ^ Kouros-Mehr H, Bechis SK, Slorach EM, Littlepage LE, Egeblad M, Ewald AJ, Pai SY, Ho IC, Werb Z (Feb 2008). "GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model". Cancer Cell. 13 (2): 141–52. doi:10.1016/j.ccr.2008.01.011. PMC 2262951free to read. PMID 18242514. 
  21. ^ McCune K, Bhat-Nakshatri P, Thorat MA, Nephew KP, Badve S, Nakshatri H (Jan 2010). "Prognosis of hormone-dependent breast cancers: implications of the presence of dysfunctional transcriptional networks activated by insulin via the immune transcription factor T-bet". Cancer Research. 70 (2): 685–96. doi:10.1158/0008-5472.CAN-09-1530. PMC 2807987free to read. PMID 20068169. 
  22. ^ Ono Y, Fukuhara N, Yoshie O (Dec 1998). "TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3". Molecular and Cellular Biology. 18 (12): 6939–50. PMC 109277free to read. PMID 9819382. 
  23. ^ Ono Y, Fukuhara N, Yoshie O (Feb 1997). "Transcriptional activity of TAL1 in T cell acute lymphoblastic leukemia (T-ALL) requires RBTN1 or -2 and induces TALLA1, a highly specific tumor marker of T-ALL". The Journal of Biological Chemistry. 272 (7): 4576–81. doi:10.1074/jbc.272.7.4576. PMID 9020185. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.