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Gata3

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Gata3

GATA binding protein 3
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; HDR; HDRS
External IDs GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Trans-acting T-cell-specific transcription factor GATA-3 is a protein that in humans is encoded by the GATA3 gene.[1][2][3]

Contents

  • Function 1
  • Clinical significance 2
    • In breast cancer 2.1
  • Interactions 3
  • See also 4
  • References 5
  • Further reading 6
  • External links 7

Function

GATA-3 belongs to the GATA family of transcription factors. It regulates luminal epithelial cell differentiation in the mammary gland.[4] 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 T cell subtype while suppressing their differentiation towards Th1 cells.[5] It is hypothesised that GATA-3 may play tissue-specific roles.[6]

Clinical significance

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

In breast cancer

GATA-3 is one of the three genes mutated in >10% of breast cancers (Cancer Genome Atlas).[7]

GATA-3 was shown to be required for the luminal A type of breast cancer, intertwined in pathways with ERα[8][9] but also androgen receptor signaling in ER-/AR+ tumors.[10]

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.[11] It is highly coexpressed with FOXA1 and serves as negative predictor of basal subtype and ERBB2 subtype.[10][12][13] GATA-3 was shown to directly regulate luminal cell differentiation in mouse models of breast cancer.[14] It is also considered a strong predictor of taxane and platin salts insensitivity.

Insulin has been shown in experimental models to downregulate expression of GATA3 by causing overexpression of T-bet, resulting in resistance to endocrine therapy.[15]

Interactions

GATA3 has been shown to interact with LMO1,[16][17] ER and FOXA1.[13]

See also

References

  1. ^ Joulin V, Bories D, Eleouet JF, Labastie MC, Chretien S, Mattei MG, Romeo PH (Jul 1991). "A T-cell specific TCR delta DNA binding protein is a member of the human GATA family". EMBO J 10 (7): 1809–16.  
  2. ^ 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". J Biol Chem 279 (26): 26983–90.  
  3. ^ "Entrez Gene: GATA3 GATA binding protein 3". 
  4. ^ Kouros-Mehr Hosein, Slorach EM, Sternlicht MD, Werb Z (December 2006). "GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland". Cell 127 (5): 1041–55.  
  5. ^ Int Immunol. 2011 Jul;23(7):415-20. doi: 10.1093/intimm/dxr029. Epub 2011 Jun 1. An updated view on transcription factor GATA3-mediated regulation of Th1 and Th2 cell differentiation. Yagi R, Zhu J, Paul WE.
  6. ^ Wilson BJ (2008). "Does GATA3 act in tissue-specific pathways? A meta-analysis-based approach". J. Carcinogenesis 7: 6.  
  7. ^ Koboldt DC, Fulton RS, McLellan MD, et al. (September 2012). "Comprehensive molecular portraits of human breast tumours". Nature 490 (7418).  
  8. ^ Wilson BJ, Giguere V (2008). "Meta-analysis of human cancer microarrays reveals that GATA3 is integral to the estrogen receptor alpha pathway". Mol Cancer 7: 49.  
  9. ^ 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.  
  10. ^ 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.  
  11. ^ Kouros-Mehr Hosein, Kim JW, Bechis SK, Werb Z (April 2008). "GATA-3 and the regulation of the mammary luminal cell fate". Curr. Opin. Cell Biol. 20 (2): 164–70.  
  12. ^ 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 Res. 11 (2): R23.  
  13. ^ 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 Res. 11 (3): R40.  
  14. ^ Kouros-Mehr Hosein, Bechis SK, Slorach EM, Littlepage LE, Egeblad M, Ewald AJ, Pai SY, Ho IC, Werb Z (February 2008). "GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model". Cancer Cell 13 (2): 141–52.  
  15. ^ McCune K, Bhat-Nakshatri P, Thorat MA, Nephew KP, Badve S, Nakshatri H (January 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 Res. 70 (2): 685–96.  
  16. ^ Ono Y, Fukuhara N, Yoshie O (December 1998). "TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3". Mol. Cell. Biol. 18 (12): 6939–50.  
  17. ^ Ono Y, Fukuhara N, Yoshie O (February 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". J. Biol. Chem. 272 (7): 4576–81.  

Further reading

  • Naylor MJ, Ormandy CJ (2007). "Gata-3 and mammary cell fate". Breast Cancer Res. 9 (2): 302.  
  • Ho IC, Vorhees P, Marin N, et al. (1991). "Human GATA-3: a lineage-restricted transcription factor that regulates the expression of the T cell receptor alpha gene". EMBO J. 10 (5): 1187–92.  
  • Marine J, Winoto A (1991). "The human enhancer-binding protein Gata3 binds to several T-cell receptor regulatory elements". Proc. Natl. Acad. Sci. U.S.A. 88 (16): 7284–8.  
  • Ko LJ, Yamamoto M, Leonard MW, et al. (1991). "Murine and human T-lymphocyte GATA-3 factors mediate transcription through a cis-regulatory element within the human T-cell receptor delta gene enhancer". Mol. Cell. Biol. 11 (5): 2778–84.  
  • Siegel MD, Zhang DH, Ray P, Ray A (1995). "Activation of the interleukin-5 promoter by cAMP in murine EL-4 cells requires the GATA-3 and CLE0 elements". J. Biol. Chem. 270 (41): 24548–55.  
  • Labastie MC, Bories D, Chabret C, et al. (1994). "Structure and expression of the human GATA3 gene". Genomics 21 (1): 1–6.  
  • Ono Y, Fukuhara N, Yoshie O (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". J. Biol. Chem. 272 (7): 4576–81.  
  • Ono Y, Fukuhara N, Yoshie O (1998). "TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3". Mol. Cell. Biol. 18 (12): 6939–50.  
  • Yang GP, Ross DT, Kuang WW, et al. (1999). "Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes". Nucleic Acids Res. 27 (6): 1517–23.  
  • Blumenthal SG, Aichele G, Wirth T, et al. (1999). "Regulation of the human interleukin-5 promoter by Ets transcription factors. Ets1 and Ets2, but not Elf-1, cooperate with GATA3 and HTLV-I Tax1". J. Biol. Chem. 274 (18): 12910–6.  
  • Van Esch H, Groenen P, Nesbit MA, et al. (2000). "GATA3 haplo-insufficiency causes human HDR syndrome". Nature 406 (6794): 419–22.  
  • Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95.  
  • Muroya K, Hasegawa T, Ito Y, et al. (2001). "GATA3 abnormalities and the phenotypic spectrum of HDR syndrome". J. Med. Genet. 38 (6): 374–80.  
  • Crawford SE, Qi C, Misra P, et al. (2002). "Defects of the heart, eye, and megakaryocytes in peroxisome proliferator activator receptor-binding protein (PBP) null embryos implicate GATA family of transcription factors". J. Biol. Chem. 277 (5): 3585–92.  
  • Kieffer LJ, Greally JM, Landres I, et al. (2002). "Identification of a candidate regulatory region in the human CD8 gene complex by colocalization of DNase I hypersensitive sites and matrix attachment regions which bind SATB1 and GATA-3". J. Immunol. 168 (8): 3915–22.  
  • Asnagli H, Afkarian M, Murphy KM (2002). "Cutting edge: Identification of an alternative GATA-3 promoter directing tissue-specific gene expression in mouse and human". J. Immunol. 168 (9): 4268–71.  
  • Steenbergen RD, OudeEngberink VE, Kramer D, et al. (2002). "Down-regulation of GATA-3 expression during human papillomavirus-mediated immortalization and cervical carcinogenesis". Am. J. Pathol. 160 (6): 1945–51.  
  • Höfer T, Nathansen H, Löhning M, et al. (2002). "GATA-3 transcriptional imprinting in Th2 lymphocytes: a mathematical model". Proc. Natl. Acad. Sci. U.S.A. 99 (14): 9364–8.  
  • Karunaratne A, Hargrave M, Poh A, Yamada T (2002). "GATA proteins identify a novel ventral interneuron subclass in the developing chick spinal cord". Dev. Biol. 249 (1): 30–43.  

External links

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