Research progress in transfactor PITX2

Abstract

Abstract: PITX2 is a member of bicoid transcriptional factor family.The PTX subfamily is composed by PITX2 and two other homologous proteins, PITX1 and PITX3.This article reviews the structure, expression and function of PITX2, the relationship between PITX2 andWnt β-catenin signal pathway.Meanwhile, the genetic diseases resulted by mutations of PITX2 and the molecular mechanisms have also been reviewed.

Key words: PITX2, transcriptional factor, structure, function, mutation

CLC Number:

R968

WANG Guo, LI Zhi, ZHOU Hong-Hao. Research progress in transfactor PITX2[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(2): 121-125.

References

[1] Semina EV, Reiter R, Leysens NJ, et al.Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome [J].Nat Genet, 1996, 14(4):392-399.
[2] lamonerie T, Tremblay JJ, Lanctôt C, et al.Ptx1, a bicoid-related homeo box transcription factor involved in transcription of the pro-opiomelanocortin gene[J].Genes Dev, 1996, 10(10):1284-1295.
[3] Gage PJ, Camper SA.Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox genes, is a potential regulator of anterior structure formation[J]. Hum Mol Genet, 1997, 6(3):457-464.
[4] Cox CJ, Espinoza HM, McWilliams B, et al.Deffential regulation of gene expression by PITX2 isoforms[J].J Bio Chem, 2002, 277(28):25001-25010.
[5] Gehring WJ.Guidebook to the homebox genes[M] Duboule D, Ed.Oxford:Oxford University Press, 1994: pp25-42.
[6] Buerglin TR., 请加具体章节名称Duboule D, Ed. Guidebook to the homebox genes.Oxford:Oxford University Press, 1994:pp43-72.
[7] Gehring WJ, Hiromi Y.Homeotic genes and the homeobox[J].Annu Rev Genet, 1986, 20:147-173.
[8] Hanes SD, Brent R.DNA specificity of the bicoid activator protein is determined by homeodomain recognition helix residue 9[J].Cell, 1989, 57(7):1275-1283.
[9] Jin Y, Hoskins R, Horvitz HR.Control of type-D GABAergic neuron differentiantion by C.elegans UNC-30 homeodomain protein[J].Nature, 1994, 372(6508):780-783.
[10] Simeone A, Acampora D, Mallamaci A, et al.A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo[J].EMBOJ, 1993, 12 (7):2735-2747.
[11] Furukawa T, Kozak CA, Cepko CL.Rax, a novel pairedtype homeobox gene, shows expression in the anterior neural fold and developing retina[J].Proc Natl Acad Sci USA, 1997, 94(7):3088-3093.
[12] Amendt BA, Sutherland LB, Russo AF.Mutifuntional role of the PITX2 homeodomain protein C-terminal tail[J].Mol Cell Bio, 1999, 19(10):7001-7010.
[13] Gage PJ, Camper SA.Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox genes, is a potential regulator of anterior structure formation[J]. Hum Mol Genet, 1997, 6(3):457-464.
[14] St.Amand TR, Ra J, Zhang Y, et al.Cloning and expression pattern of chicken PITX2:a new component in the shh signaling pathway controlling embryonic heart looping [J].Biochem Biophys Res Commun, 1998, 247(1):100-105.
[15] Campione M, Steinbeisser H, Schweickert A, et al.The homeobox gene PITX2:mediator of asymmetric left-right signaling in vertebrate heart and gut looping[J].Dev, 1999, 126(6):1224-1234.
[16] Lin CR, Kioussi C, O'Connell S, et al.Pitx2 regulates lung asymmetry, cardiac positioning and pituitary and tooth morphogenesis[J].Nature, 1999, 401(6750):279-282.
[17] Cadigan KM, Nusse R.Wnt signaling:a common theme in animal development[J].Genes Dev, 1997, 11(24): 3286-3305.
[18] Kioussi C, Briata P, Baek SH, et al.Identification of a Wnt Dvl β-catenin →PITX2 pathway mediating cell-typespecific proliferation during development[J].Cell, 2002, 111(5):673-685.
[19] Briata P, Ilengo C, Corte G, et al.The Wnt β-catenin →PITX2 pathway controls the turnover of PITX2 and other unstable mRNAs[J].Mol Cell, 2003, 12(5):1201-1211.
[20] Pearce WG, Wyatt HT, Boyd TA, et al.Autosomal dominant iridogoniody sgenesis.A genetic and clinical study [J].Birth Defects Orig Artic Ser, 1982, 18(6):561-569.
[21] Kozlowski K, Walter MA.Variation in residual PITX2 activity underlies the phenotypic spectrum of anterior segment developmental disorders[J].Hum Mol Genet, 2000, 9 (14):2131-2139.
[22] Saadi I, Kuburas A, Engle JJ, et al.Dominant negative dimerizationg of a mutant homeodomain protein in Axenfeld-Rieger syndrome[J].Mol Cell Bio, 2003, 23(6): 1968-1982.
[23] Mattos J, Contreras F, O'Donnell FE.Ring dermoid syndrome:A new syndrome of autosomal dominantly inherited, bilateral, annular limbal dermoids with corneal and conjunctival extension[J].Arch Ophthalmol, 1980, 98 (6):1059-1061.
[24] Xia K, Wu LQ, Liu XP, et al.Mutation in PITX2 is associated with ring dermoid of the cornea[J].JMed Genet, 2004, 41(12):e129.
[25] Wang G, Liu XP, Qian P, et al.Functional analysis of three genetic disorder related PITX2 mutants[J].Chinese science bulletin, 2006, 51(2):164-169.
[26] 刘小平, 朱飞舟, 王果, 等.PITX2 R62H 突变导致角膜环状皮样瘤的分子基础[J].生物化学与生物物理进展, 2008, 35(3):274-282.