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Gene Review

PITX1  -  paired-like homeodomain 1

Homo sapiens

Synonyms: BFT, CCF, Hindlimb-expressed homeobox protein backfoot, Homeobox protein PITX1, LBNBG, ...
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Disease relevance of PITX1

  • Restoration of PITX1 in the colon cancer cells inhibited tumorigenicity in a wild-type RAS-dependent manner [1].
  • In contrast, PITX1 mRNA expression is decreased in Barrett's esophagus, compared with matching normal squamous esophagus specimens, and is further decreased in Barrett's-associated cancer [2].
  • Thus, there was no relationship between Ptx1 expression and a particular type of pituitary adenomas [3].
  • Modulation of interferon expression by hepatitis C virus NS5A protein and human homeodomain protein PTX1 [4].
  • Expression of Tpit and Pitx1 genes in most carcinoids suggests that some aspects of the pituitary corticotroph phenotype may belong to general carcinoid differentiation [5].

Psychiatry related information on PITX1

  • Of these, 14 families underwent a psycho-educative intervention programme called BFT (Behavioural Family Therapy) [6].

High impact information on PITX1

  • Thus, PITX1 suppresses tumorigenicity by downregulating the RAS pathway through RASAL1 [1].
  • Interestingly, we observed low expression of PITX1 in prostate and bladder tumors and in colon cancer cell lines containing wild-type RAS [1].
  • REST is a transcriptional repressor that silences neuron-specific gene expression, and PITX1 is a homeodomain transcription factor that promotes the expression of a negative regulator of Ras [7].
  • Role of Pitx1 upstream of Tbx4 in specification of hindlimb identity [8].
  • Ptx1 (Pitx1) is a bicoid-related homeobox transcription factor expressed from the onset of pituitary development [9].

Chemical compound and disease context of PITX1

  • Strains of Bacteroides fragilis associated with diarrheal disease (enterotoxigenic B. fragilis) produce a 20-kDa zinc-dependent metalloprotease toxin (B. fragilis enterotoxin; BFT) that reversibly stimulates chloride secretion and alters tight junctional function in polarized intestinal epithelial cells [10].
  • Inhibitors of endosomal and Golgi trafficking (NH4Cl and brefeldin A) prevented the intoxication of HT29/C1 cells by Clostridium difficile toxin A and cholera toxin, respectively, but not by BFT [11].
  • Furthermore, SB203580 prevented BFT-induced colitis in the mouse ileum, as evidenced by significant decreases in villous destruction, neutrophil infiltration, and mucosal congestion [12].

Biological context of PITX1

  • Increased CDX2 and decreased PITX1 homeobox gene expression in Barrett's esophagus and Barrett's-associated adenocarcinoma [2].
  • Using in vitro binding assays and a series of site-specific mutations of the proximal hPRL promoter, we mapped the B1 and B2 bicoid sites involved in Pitx-mediated transactivation of the hPRL-164luc construct [13].
  • Altogether, these results suggest that full responsiveness to several signaling pathways regulating the hPRL promoter requires the B2 Pitx binding site and that Pitx factors may be part of the proteic complex involved in these regulations [13].
  • Computer analysis revealed the presence of Ptx1/Pitx1 signal sequences within the promoter region of human 11beta hydroxylase ( hCYP11B1) [14].
  • In mice, Ptx1 and Ptx2 gene expression has been detected in the area of the pituitary primordium and is maintained throughout development in Rathke pouch and adult pituitary [15].

Anatomical context of PITX1

  • Therefore, we analyzed the presence and role of Ptx1/Pitx1 in human adrenal cortex [14].
  • Northern hybridization analysis of RNAs from human tissues revealed that human BFT is highly expressed in adult skeletal muscle and bladder [16].
  • The Pitx homeobox gene family has important roles in vertebrate pituitary, eye, branchial arch, hindlimb and brain development, as well as a key function in regulating left-right asymmetry [17].
  • Misexpression of Pitx1 in the forelimb results in the transformation and translocation of specific muscles, tendons, and bones of the forelimb so that they acquire a hindlimb-like morphology [18].
  • Pitx1 determines the morphology of muscle, tendon, and bones of the hindlimb [18].

Associations of PITX1 with chemical compounds

  • In addition, mutation in the B2 Pitx site results in attenuation of the promoter's responsiveness to forskolin, thyrotropin-releasing hormone, and epidermal growth factor [13].
  • Pituitary homeobox factor 1, a novel transcription factor in the adrenal regulating steroid 11beta-hydroxylase [14].
  • We demonstrate here that Pitx-1 plays a crucial role in the regulation of the Chinook salmon luteinizing hormone beta gene promoter through a number of novel mechanisms [19].
  • The time required for the association of BFT with HT29/C1 cells at 4 degrees C was inversely correlated with concentration [11].
  • In addition, a selective COX-2 inhibitor, NS-398, significantly inhibited the increased cAMP level induced by BFT stimulation [20].
  • Both PITX1 and PITX2C interacted with Smad3 (an effector of the activin signaling cascade in these cells) in coprecipitation experiments, and the PITX binding site mutation greatly inhibited Smad2/3/4-stimulated Fshb transcription [21].

Regulatory relationships of PITX1

  • Interestingly, the NeuroD1 heterodimers activate transcription in synergy with Ptx1, a Bicoid-related homeodomain protein, which also contributes to corticotroph specificity of POMC transcription [22].
  • However, despite multiple putative E-boxes in the MT(1) promoter, transfected Clock and Bmal1 were unable to regulate either basal or Pitx-1-stimulated MT(1) promoter activity [23].

Other interactions of PITX1


Analytical, diagnostic and therapeutic context of PITX1


  1. A genetic screen identifies PITX1 as a suppressor of RAS activity and tumorigenicity. Kolfschoten, I.G., van Leeuwen, B., Berns, K., Mullenders, J., Beijersbergen, R.L., Bernards, R., Voorhoeve, P.M., Agami, R. Cell (2005) [Pubmed]
  2. Increased CDX2 and decreased PITX1 homeobox gene expression in Barrett's esophagus and Barrett's-associated adenocarcinoma. Lord, R.V., Brabender, J., Wickramasinghe, K., DeMeester, S.R., Holscher, A., Schneider, P.M., Danenberg, P.V., DeMeester, T.R. Surgery (2005) [Pubmed]
  3. Expression of pituitary homeo box 1 (Ptx1) in human non-neoplastic pituitaries and pituitary adenomas. Tahara, S., Kurotani, R., Sanno, N., Takumi, I., Yoshimura, S., Osamura, R.Y., Teramoto, A. Mod. Pathol. (2000) [Pubmed]
  4. Modulation of interferon expression by hepatitis C virus NS5A protein and human homeodomain protein PTX1. Ghosh, A.K., Majumder, M., Steele, R., Ray, R., Ray, R.B. Virology (2003) [Pubmed]
  5. RT-PCR analysis of corticotroph-associated genes expression in carcinoid tumours in the ectopic-ACTH syndrome. Messager, M., Carrière, C., Bertagna, X., de Keyzer, Y. Eur. J. Endocrinol. (2006) [Pubmed]
  6. Family intervention in schizophrenia--impact on family burden and attitude. Berglund, N., Vahlne, J.O., Edman, A. Social psychiatry and psychiatric epidemiology. (2003) [Pubmed]
  7. RNA interference libraries prove their worth in hunt for tumor suppressor genes. Downward, J. Cell (2005) [Pubmed]
  8. Role of Pitx1 upstream of Tbx4 in specification of hindlimb identity. Logan, M., Tabin, C.J. Science (1999) [Pubmed]
  9. Ptx1 regulates SF-1 activity by an interaction that mimics the role of the ligand-binding domain. Tremblay, J.J., Marcil, A., Gauthier, Y., Drouin, J. EMBO J. (1999) [Pubmed]
  10. Bacteroides fragilis enterotoxin cleaves the zonula adherens protein, E-cadherin. Wu, S., Lim, K.C., Huang, J., Saidi, R.F., Sears, C.L. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  11. Bacteroides fragilis toxin rapidly intoxicates human intestinal epithelial cells (HT29/C1) in vitro. Saidi, R.F., Sears, C.L. Infect. Immun. (1996) [Pubmed]
  12. Mitogen-activated protein kinase and activator protein-1 dependent signals are essential for Bacteroides fragilis enterotoxin-induced enteritis. Kim, J.M., Jung, H.Y., Lee, J.Y., Youn, J., Lee, C.H., Kim, K.H. Eur. J. Immunol. (2005) [Pubmed]
  13. Pitx factors are involved in basal and hormone-regulated activity of the human prolactin promoter. Quentien, M.H., Manfroid, I., Moncet, D., Gunz, G., Muller, M., Grino, M., Enjalbert, A., Pellegrini, I. J. Biol. Chem. (2002) [Pubmed]
  14. Pituitary homeobox factor 1, a novel transcription factor in the adrenal regulating steroid 11beta-hydroxylase. Hiroi, N., Kino, T., Bassett, M., Rainey, W.E., Phung, M., Abu-Asab, M., Fojo, T., Briata, P., Chrousos, G.P., Bornstein, S.R. Horm. Metab. Res. (2003) [Pubmed]
  15. Expression of the members of the Ptx family of transcription factors in human pituitary adenomas. Pellegrini-Bouiller, I., Manrique, C., Gunz, G., Grino, M., Zamora, A.J., Figarella-Branger, D., Grisoli, F., Jaquet, P., Enjalbert, A. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  16. Backfoot is a novel homeobox gene expressed in the mesenchyme of developing hind limb. Shang, J., Luo, Y., Clayton, D.A. Dev. Dyn. (1997) [Pubmed]
  17. Cloning and expression of a Pitx homeobox gene from the lamprey, a jawless vertebrate. Boorman, C.J., Shimeld, S.M. Dev. Genes Evol. (2002) [Pubmed]
  18. Pitx1 determines the morphology of muscle, tendon, and bones of the hindlimb. Delaurier, A., Schweitzer, R., Logan, M. Dev. Biol. (2006) [Pubmed]
  19. Multiple mechanisms for Pitx-1 transactivation of a luteinizing hormone beta subunit gene. Melamed, P., Koh, M., Preklathan, P., Bei, L., Hew, C. J. Biol. Chem. (2002) [Pubmed]
  20. Bacteroides fragilis enterotoxin induces cyclooxygenase-2 and fluid secretion in intestinal epithelial cells through NF-kappaB activation. Kim, J.M., Lee, J.Y., Yoon, Y.M., Oh, Y.K., Kang, J.S., Kim, Y.J., Kim, K.H. Eur. J. Immunol. (2006) [Pubmed]
  21. Paired-like homeodomain transcription factors 1 and 2 regulate follicle-stimulating hormone beta-subunit transcription through a conserved cis-element. Lamba, P., Khivansara, V., D'Alessio, A.C., Santos, M.M., Bernard, D.J. Endocrinology (2008) [Pubmed]
  22. NeuroD1/beta2 contributes to cell-specific transcription of the proopiomelanocortin gene. Poulin, G., Turgeon, B., Drouin, J. Mol. Cell. Biol. (1997) [Pubmed]
  23. Regulation of the ovine MT(1) melatonin receptor promoter: Interaction between multiple pituitary transcription factors at different phases of development. Johnston, J.D., Schuster, C., Barrett, P., Hazlerigg, D.G. Mol. Cell. Endocrinol. (2007) [Pubmed]
  24. Xpitx3: a member of the Rieg/Pitx gene family expressed during pituitary and lens formation in Xenopus laevis. Pommereit, D., Pieler, T., Hollemann, T. Mech. Dev. (2001) [Pubmed]
  25. Familial combined pituitary hormone deficiency caused by PROP-1 gene mutation. Growth patterns and MRI studies in untreated subjects. Crone, J., Pfäffle, R., Stobbe, H., Prayer, D., Gomez, I., Frisch, H. Horm. Res. (2002) [Pubmed]
  26. Backfoot, a novel homeobox gene, maps to human chromosome 5 (BFT) and mouse chromosome 13 (Bft). Shang, J., Li, X., Ring, H.Z., Clayton, D.A., Francke, U. Genomics (1997) [Pubmed]
  27. Human and murine PTX1/Ptx1 gene maps to the region for Treacher Collins syndrome. Crawford, M.J., Lanctôt, C., Tremblay, J.J., Jenkins, N., Gilbert, D., Copeland, N., Beatty, B., Drouin, J. Mamm. Genome (1997) [Pubmed]
  28. IDN5109, a taxane with oral bioavailability and potent antitumor activity. Nicoletti, M.I., Colombo, T., Rossi, C., Monardo, C., Stura, S., Zucchetti, M., Riva, A., Morazzoni, P., Donati, M.B., Bombardelli, E., D'Incalci, M., Giavazzi, R. Cancer Res. (2000) [Pubmed]
  29. Bacteroides fragilis toxin exhibits polar activity on monolayers of human intestinal epithelial cells (T84 cells) in vitro. Chambers, F.G., Koshy, S.S., Saidi, R.F., Clark, D.P., Moore, R.D., Sears, C.L. Infect. Immun. (1997) [Pubmed]
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