Encyclopedia of Signaling Molecules

2012 Edition
| Editors: Sangdun Choi

Prep

  • Giorgio Iotti
  • Francesco Blasi
Reference work entry
DOI: https://doi.org/10.1007/978-1-4419-0461-4_549

Synonyms

 PKNOX

Historical Background

PREP1 (named PKNOX1, Pbx/KNOX 1) was identified by Chen et al. (1997) in their effort to characterize genes mapping in the human chromosome 21. At the same time, PREP1 was identified as one of the components of the human transcription factor complex UEF3, urokinase enhancer factor 3. Prep1 was found to be a homeodomain-containing DNA-binding protein belonging to the TALE (Three Aminoacid Loop Extension) superclass, most closely related to TGIF (TGF β–induced factor homeobox) and Meis1 (Meis homeobox 1) and recognizing the TGACAG motif. Furthermore, it has been demonstrated that Prep1 heterodimerizes with Pbx, enhancing its affinity and DNA-binding specificity to include both the TGACAG and the TGATNNAT motifs (hence the acronym, for Pbx regulating protein 1) (Berthelsen et al. 1998).

PREP2 was identified by Imoto et al. (2001) as a TALE homeodomain-encoding gene, located at 11q24 in the human genome.

Gene and Protein Structure

The human PREP1 gene...

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References

  1. Bailey JS, Rave-Harel N, McGillivray SM, Coss D, Mellon PL. Activin regulation of the follicle-stimulating hormone beta-subunit gene involves Smads and the TALE homeodomain proteins Pbx1 and Prep1. Mol Endocrinol. 2004;18:1158–70.PubMedGoogle Scholar
  2. Berthelsen J, Zappavigna V, Mavilio F, Blasi F. Prep1, a novel functional partner of Pbx proteins. EMBO J. 1998;17:1423–33.PubMedGoogle Scholar
  3. Berthelsen J, Kilstrup-Nielsen C, Blasi F, Mavilio F, Zappavigna V. The subcellular localization of PBX1 and EXD proteins depends on nuclear import and export signals and is modulated by association with PREP1 and HTH. Genes Dev. 1999;13:946–53.PubMedGoogle Scholar
  4. Chen H, Rossier C, Nakamura Y, Lynn A, Chakravarti A, Antonarakis SE. Cloning of a novel homeobox-containing gene, PKNOX1, and mapping to human chromosome 21q22.3. Genomics 1997;41:193–200.Google Scholar
  5. Díaz VM, Mori S, Longobardi E, Menendez G, Ferrai C, Keough RA, et al. p160 Myb-binding protein interacts with Prep1 and inhibits its transcriptional activity. Mol Cell Biol. 2007;27:7981–90.PubMedGoogle Scholar
  6. Di Rosa P, Villaescusa JC, Longobardi E, Iotti G, Ferretti E, Diaz VM, et al. The homeodomain transcription factor Prep1 (pKnox1) is required for hematopoietic stem and progenitor cell activity. Dev Biol. 2007;311:324–34.PubMedGoogle Scholar
  7. Fernandez-Diaz LC, Laurent A, Girasoli S, Turco M, Longobardi E, Iotti G, et al. The absence of Prep1 causes p53-dependent apoptosis of pluripotent epiblast cells. Development. 2010;137:3393–403.PubMedGoogle Scholar
  8. Ferretti E, Schulz H, Talarico D, Blasi F, Berthelsen J. The PBX-regulating protein PREP1 is present in different PBX-complexed forms in mouse. Mech Dev. 1999;83:53–64.PubMedGoogle Scholar
  9. Ferretti E, Marshall H, Pöpperl H, Maconochie M, Krumlauf R, Blasi F. A complex site including both Pbx-Hox and Prep-Meis-responsive elements and binding a retinoic acid-inducible ternary Hoxb1-Pbx-Prep1 complex is required for HOXB2 rhombomere 4 expression. Development. 2000;127:155–66.PubMedGoogle Scholar
  10. Ferretti E, Villaescusa JC, Di Rosa P, Fernandez-Diaz LC, Longobardi E, Mazzieri R, et al. Hypomorphic mutation of the TALE gene Prep1 (pKnox1) causes a major reduction of Pbx and Meis proteins and a pleiotropic embryonic phenotype. Mol Cell Biol. 2006;26:5650–62.PubMedGoogle Scholar
  11. Fognani C, Kilstrup-Nielsen C, Berthelsen J, Ferretti E, Zappavigna V, Blasi F. Characterization of PREP2, a paralog of PREP1, which defines a novel sub-family of the MEINOX TALE homeodomain transcription factors. Nucleic Acids Res. 2002;30:2043–51.PubMedGoogle Scholar
  12. Goudet G, Delhalle S, Biemar F, Martial JA, Peers B. Functional and Cooperative Interactions between the Homeodomain PDX1, Pbx, and Prep1 Factors on the Somatostatin Promoter J Biol Chem. 1999;274:4067–73.Google Scholar
  13. Haller K, Rambaldi I, Kovacs EN, Daniels E, Featherstone M. Prep2: cloning and expression of a new prep family member. Dev Dyn. 2002;225:358–64.PubMedGoogle Scholar
  14. Haller K, Rambaldi I, Daniels E, Featherstone M. Subcellular localization of multiple PREP2 isoforms is regulated by actin, tubulin, and nuclear export. J Biol Chem. 2004;279:49384–94.PubMedGoogle Scholar
  15. Imoto I, Sonoda I, Yuki Y, Inazawa J. Identification and characterization of human PKNOX2, a novel homeobox-containing gene. Biochem Biophys Res Commun. 2001;287:270–6.PubMedGoogle Scholar
  16. Longobardi E, Iotti G, Di Rosa P, Mejetta S, Bianchi F, Fernandez-Diaz LC, et al. Spontaneous tumor development and acceleration of EmMyc lymphomas in mice haploinsufficient for the homeodomain transcription factor gene Prep1 (pKnox1) indicates a tumor suppressor function. Mol Oncol. 2010;4:226–34.Google Scholar
  17. Mikkola I, Bruun JA, Holm T, Johansen T. Superactivation of Pax6-mediated transactivation from paired domain-binding sites by DNA-independent recruitment of different homeodomain proteins. J Biol Chem. 2001;276:4109–18.PubMedGoogle Scholar
  18. Moens CB, Selleri L. Hox cofactors in vertebrate development. Dev Biol. 2006;291:193–206.PubMedGoogle Scholar
  19. Mukherjee K, Bürglin TR. Comprehensive analysis of animal TALE homeobox genes: new conserved motifs and cases of accelerated evolution. J Mol Evol. 2007;65:137–53.PubMedGoogle Scholar
  20. Rowan S, Siggers T, Lachke SA, Yue Y, Bulyk ML, Maas RL. Precise temporal control of the eye regulatory gene Pax6 via enhancer-binding site affinity. Genes Dev. 2010;24:980–5.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.IFOM (Fondazione Istituto FIRC di Oncologia Molecolare)MilanItaly