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Biochem J. Aug 15, 2002; 366(Pt 1): 367–375.
PMCID: PMC1222745

OTEX, an androgen-regulated human member of the paired-like class of homeobox genes.


paired genes emerged early in evolution and code for homeobox transcription factors, having fundamental roles in various biological processes. We identified a novel human member of the paired-like class, which we named OTEX. A phylogenetic analysis revealed that OTEX belonged to the recently defined PEPP subfamily of paired-like homeobox genes. It was organized into three introns and, like the other PEPP genes, it was mapped to chromosome X. Its transcripts were detected mainly in the ovary, testis and epididymis, but also in the prostate and mammary gland. In the PC-3/ARwt prostate cell line, OTEX expression was stimulated dramatically following androgen treatment. Immunofluorescence studies revealed an exclusively nuclear localization of the OTEX protein. Mutation of the RARCRRHQRE amino acid sequence present at the C-terminus of the OTEX homeodomain resulted in a mainly cytoplasmic localization, indicating that this motif harboured the nuclear localization signal. No inherent transactivation function was seen for OTEX using the one-hybrid assay, and no homodimer formation was observed in the two-hybrid assay, suggesting that additional partners were needed for this activity. Taken together, the data show that OTEX represents a novel, androgen-regulated, paired-like homeobox protein, with possibly an important role in human reproduction.

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Selected References

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  • Treisman J, Harris E, Wilson D, Desplan C. The homeodomain: a new face for the helix-turn-helix? Bioessays. 1992 Mar;14(3):145–150. [PubMed]
  • Gehring WJ, Affolter M, Bürglin T. Homeodomain proteins. Annu Rev Biochem. 1994;63:487–526. [PubMed]
  • Torres M, Gómez-Pardo E, Dressler GR, Gruss P. Pax-2 controls multiple steps of urogenital development. Development. 1995 Dec;121(12):4057–4065. [PubMed]
  • Birk OS, Casiano DE, Wassif CA, Cogliati T, Zhao L, Zhao Y, Grinberg A, Huang S, Kreidberg JA, Parker KL, et al. The LIM homeobox gene Lhx9 is essential for mouse gonad formation. Nature. 2000 Feb 24;403(6772):909–913. [PubMed]
  • Satokata I, Benson G, Maas R. Sexually dimorphic sterility phenotypes in Hoxa10-deficient mice. Nature. 1995 Mar 30;374(6521):460–463. [PubMed]
  • Gendron RL, Paradis H, Hsieh-Li HM, Lee DW, Potter SS, Markoff E. Abnormal uterine stromal and glandular function associated with maternal reproductive defects in Hoxa-11 null mice. Biol Reprod. 1997 May;56(5):1097–1105. [PubMed]
  • Galliot B, de Vargas C, Miller D. Evolution of homeobox genes: Q50 Paired-like genes founded the Paired class. Dev Genes Evol. 1999 Mar;209(3):186–197. [PubMed]
  • Maiti S, Meistrich ML, Wilson G, Shetty G, Marcelli M, McPhaul MJ, Morris PL, Wilkinson MF. Irradiation selectively inhibits expression from the androgen-dependent Pem homeobox gene promoter in sertoli cells. Endocrinology. 2001 Apr;142(4):1567–1577. [PubMed]
  • Sasaki AW, Doskow J, MacLeod CL, Rogers MB, Gudas LJ, Wilkinson MF. The oncofetal gene Pem encodes a homeodomain and is regulated in primordial and pre-muscle stem cells. Mech Dev. 1991 Jun;34(2-3):155–164. [PubMed]
  • Maiti S, Doskow J, Li S, Nhim RP, Lindsey JS, Wilkinson MF. The Pem homeobox gene. Androgen-dependent and -independent promoters and tissue-specific alternative RNA splicing. J Biol Chem. 1996 Jul 19;271(29):17536–17546. [PubMed]
  • Li Y, Lemaire P, Behringer RR. Esx1, a novel X chromosome-linked homeobox gene expressed in mouse extraembryonic tissues and male germ cells. Dev Biol. 1997 Aug 1;188(1):85–95. [PubMed]
  • Branford WW, Zhao GQ, Valerius MT, Weinstein M, Birkenmeier EH, Rowe LB, Potter SS. Spx1, a novel X-linked homeobox gene expressed during spermatogenesis. Mech Dev. 1997 Jul;65(1-2):87–98. [PubMed]
  • Fohn LE, Behringer RR. ESX1L, a novel X chromosome-linked human homeobox gene expressed in the placenta and testis. Genomics. 2001 May 15;74(1):105–108. [PubMed]
  • Han YJ, Park AR, Sung DY, Chun JY. Psx, a novel murine homeobox gene expressed in placenta. Gene. 1998 Jan 30;207(2):159–166. [PubMed]
  • Han YJ, Lee YH, Chun JY. Identification and characterization of Psx-2, a novel member of the Psx (placenta-specific homeobox) family. Gene. 2000 Jan 4;241(1):149–155. [PubMed]
  • Takasaki N, McIsaac R, Dean J. Gpbox (Psx2), a homeobox gene preferentially expressed in female germ cells at the onset of sexual dimorphism in mice. Dev Biol. 2000 Jul 1;223(1):181–193. [PubMed]
  • Pitman JL, Lin TP, Kleeman JE, Erickson GF, MacLeod CL. Normal reproductive and macrophage function in Pem homeobox gene-deficient mice. Dev Biol. 1998 Oct 15;202(2):196–214. [PubMed]
  • Takasaki N, Rankin T, Dean J. Normal gonadal development in mice lacking GPBOX, a homeobox protein expressed in germ cells at the onset of sexual dimorphism. Mol Cell Biol. 2001 Dec;21(23):8197–8202. [PMC free article] [PubMed]
  • Li Y, Behringer RR. Esx1 is an X-chromosome-imprinted regulator of placental development and fetal growth. Nat Genet. 1998 Nov;20(3):309–311. [PubMed]
  • Miller DJ, Hayward DC, Reece-Hoyes JS, Scholten I, Catmull J, Gehring WJ, Callaerts P, Larsen JE, Ball EE. Pax gene diversity in the basal cnidarian Acropora millepora (Cnidaria, Anthozoa): implications for the evolution of the Pax gene family. Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4475–4480. [PMC free article] [PubMed]
  • Breathnach R, Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. [PubMed]
  • Lo K, Smale ST. Generality of a functional initiator consensus sequence. Gene. 1996 Dec 5;182(1-2):13–22. [PubMed]
  • Barbulescu K, Geserick C, Schüttke I, Schleuning WD, Haendler B. New androgen response elements in the murine pem promoter mediate selective transactivation. Mol Endocrinol. 2001 Oct;15(10):1803–1816. [PubMed]
  • Jans DA, Xiao CY, Lam MH. Nuclear targeting signal recognition: a key control point in nuclear transport? Bioessays. 2000 Jun;22(6):532–544. [PubMed]
  • Boulikas T. Putative nuclear localization signals (NLS) in protein transcription factors. J Cell Biochem. 1994 May;55(1):32–58. [PubMed]
  • Zellmer E, Zhang Z, Greco D, Rhodes J, Cassel S, Lewis EJ. A homeodomain protein selectively expressed in noradrenergic tissue regulates transcription of neurotransmitter biosynthetic genes. J Neurosci. 1995 Dec;15(12):8109–8120. [PubMed]
  • Wimmer Katharina, Zhu Xx Xiao-xiang, Rouillard Jean Marie, Ambros Peter F, Lamb Barbara J, Kuick Rork, Eckart Markus, Weinhäusl Andreas, Fonatsch Christa, Hanash Sam M. Combined restriction landmark genomic scanning and virtual genome scans identify a novel human homeobox gene, ALX3, that is hypermethylated in neuroblastoma. Genes Chromosomes Cancer. 2002 Mar;33(3):285–294. [PubMed]
  • Wuyts W, Cleiren E, Homfray T, Rasore-Quartino A, Vanhoenacker F, Van Hul W. The ALX4 homeobox gene is mutated in patients with ossification defects of the skull (foramina parietalia permagna, OMIM 168500). J Med Genet. 2000 Dec;37(12):916–920. [PMC free article] [PubMed]
  • Rao E, Weiss B, Fukami M, Rump A, Niesler B, Mertz A, Muroya K, Binder G, Kirsch S, Winkelmann M, et al. Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. Nat Genet. 1997 May;16(1):54–63. [PubMed]
  • Maiti S, Doskow J, Sutton K, Nhim RP, Lawlor DA, Levan K, Lindsey JS, Wilkinson MF. The Pem homeobox gene: rapid evolution of the homeodomain, X chromosomal localization, and expression in reproductive tissue. Genomics. 1996 Jun 15;34(3):304–316. [PubMed]
  • Swanson WJ, Clark AG, Waldrip-Dail HM, Wolfner MF, Aquadro CF. Evolutionary EST analysis identifies rapidly evolving male reproductive proteins in Drosophila. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7375–7379. [PMC free article] [PubMed]
  • Yan YT, Stein SM, Ding J, Shen MM, Abate-Shen C. A novel PF/PN motif inhibits nuclear localization and DNA binding activity of the ESX1 homeoprotein. Mol Cell Biol. 2000 Jan;20(2):661–671. [PMC free article] [PubMed]
  • Moede T, Leibiger B, Pour HG, Berggren P, Leibiger IB. Identification of a nuclear localization signal, RRMKWKK, in the homeodomain transcription factor PDX-1. FEBS Lett. 1999 Nov 19;461(3):229–234. [PubMed]
  • Fei Y, Hughes TE. Nuclear trafficking of photoreceptor protein crx: the targeting sequence and pathologic implications. Invest Ophthalmol Vis Sci. 2000 Sep;41(10):2849–2856. [PubMed]
  • Norris RA, Kern MJ. Identification of domains mediating transcription activation, repression, and inhibition in the paired-related homeobox protein, Prx2 (S8). DNA Cell Biol. 2001 Feb;20(2):89–99. [PubMed]
  • Dasen JS, Martinez Barbera JP, Herman TS, Connell SO, Olson L, Ju B, Tollkuhn J, Baek SH, Rose DW, Rosenfeld MG. Temporal regulation of a paired-like homeodomain repressor/TLE corepressor complex and a related activator is required for pituitary organogenesis. Genes Dev. 2001 Dec 1;15(23):3193–3207. [PMC free article] [PubMed]
  • Haendler B. Androgen-selective gene regulation in the prostate. Biomed Pharmacother. 2002 Mar;56(2):78–83. [PubMed]
  • Krauss CM, Turksoy RN, Atkins L, McLaughlin C, Brown LG, Page DC. Familial premature ovarian failure due to an interstitial deletion of the long arm of the X chromosome. N Engl J Med. 1987 Jul 16;317(3):125–131. [PubMed]
  • Beverdam A, Brouwer A, Reijnen M, Korving J, Meijlink F. Severe nasal clefting and abnormal embryonic apoptosis in Alx3/Alx4 double mutant mice. Development. 2001 Oct;128(20):3975–3986. [PubMed]
  • Fromental-Ramain C, Warot X, Lakkaraju S, Favier B, Haack H, Birling C, Dierich A, Doll e P, Chambon P. Specific and redundant functions of the paralogous Hoxa-9 and Hoxd-9 genes in forelimb and axial skeleton patterning. Development. 1996 Feb;122(2):461–472. [PubMed]
  • Tanaka M, Schinke M, Liao HS, Yamasaki N, Izumo S. Nkx2.5 and Nkx2.6, homologs of Drosophila tinman, are required for development of the pharynx. Mol Cell Biol. 2001 Jul;21(13):4391–4398. [PMC free article] [PubMed]

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