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PKNOX1  -  PBX/knotted 1 homeobox 1

Homo sapiens

Synonyms: Homeobox protein PKNOX1, Homeobox protein PREP-1, PBX/knotted homeobox 1, PREP1, pkonx1c
 
 
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Disease relevance of PKNOX1

  • The involvement of the PKNOX1 gene in Down syndrome and/or monogenic disorders associated with dysfunction of this gene is presently unknown [1].
  • F9 teratocarcinoma cells stably transfected with PREP-1 had an increased DNA binding activity to a PREP-PBX-responsive element [2].
 

High impact information on PKNOX1

  • Interaction with Prep1 enhances the ability of the HOXB1-Pbx1 complex to activate transcription in a cooperative fashion from the same target [3].
  • The Prep1 homeodomain belongs to the TALE class of homeodomains, is most closely related to those of the TGIF and Meis1 proteins, and like these, recognizes a TGACAG motif [4].
  • Despite sequence similarity to MEIS and a shared ability to form heteromeric complexes with PBX and HOX partners, the PREP1 C terminus does not respond to TSA or PKA [5].
  • We show that overexpression of PREP-1 influences the level of PBX-2 protein maintaining the PREP-1-PBX balance [2].
  • Hence, dimerization with PREP-1 appears to decrease proteasomal degradation of PBX-2 [2].
 

Biological context of PKNOX1

  • Cloning of a novel homeobox-containing gene, PKNOX1, and mapping to human chromosome 21q22.3 [1].
  • This gene is named PKNOX1 by the Human Nomenclature Committee. By PCR amplification, hybridization, and genetic linkage analysis using a (GT)n polymorphism in the 3'UTR, we have precisely localized PKNOX1 to chromosome 21q22.3 between markers D21S212 and D21S25 on YAC350F7 [1].
  • Overexpression of FABP7 in Down syndrome fetal brains is associated with PKNOX1 gene-dosage imbalance [6].
  • Additionally, these data imply functional similarities and differences between PREP1 and MEIS1 in the regulation of PF4 gene expression [7].
  • Comparison between the wild-type and mutant Hoxa1 reveals that they show distinct activity on the TSEII enhancer of the somatostatin gene, but that they are equally active in the presence of Pbx and Prep cofactors [8].
 

Anatomical context of PKNOX1

 

Associations of PKNOX1 with chemical compounds

  • Indeed, PBX-2 level drastically decreased after 3 h of cycloheximide treatment in control but not in PREP-1-overexpressing cells and the proteasome inhibitor MG132 prevented PBX-2 decay in control cells [2].
  • EMSA shows that either PREP1 by itself or PREP1/PBX complexes bind to the two TGACAG motifs in the TME and activate the PF4 promoter [7].
  • METHODS: One hundred fifty consecutive patients (148 men) undergoing outpatient colonoscopy were randomly selected for one of three preparations (Prep 1: 4 L PEG-ELS; Prep 2: 2 L PEG-ELS plus 296 mL magnesium citrate 1 hour prior; Prep 3: 2 L PEG-ELS plus bisacodyl 20 mg) [11].
  • Benzoylecgonine (BZE) extraction from urine was explored using Cerex Polycrom Clin II solid-phase extraction (SPE) columns and the Speedisk 48 Pressure Processor as an alternative to the Prep1 automated sample processor and XTRX Type RP/W columns [12].
  • Reflex HPV DNA testing using Hybrid Capture II method was carried out on 88 women with ASC-H diagnosed by Thin Prep Pap test [13].
 

Physical interactions of PKNOX1

  • Functional studies showed that PBX3C and PBX3D proteins were unable to interact with the PBX-interacting factor PREP1 and weakly interacted with MEIS proteins [14].
 

Regulatory relationships of PKNOX1

  • These data demonstrate that PREP1 is also an important transcription factor that regulates PF4 gene expression such as MEIS1 [7].
  • However, PBX1 exogenously introduced into COL5A2-negative cells cannot stimulate FPB-driven transcription unless co-expressed with PREP1 [15].
 

Other interactions of PKNOX1

  • Unlike PKNOX1, which was broadly expressed in many tissues, PKNOX2 showed a more restricted pattern of mRNA expression [16].
  • The UGT2B17 Pbx site matches a consensus Pbx site known to bind members of the Pbx, Hox, Meis, and Prep1 families of homeodomain-containing proteins and has previously been shown to bind nuclear proteins in DNaseI footprint assays [17].
 

Analytical, diagnostic and therapeutic context of PKNOX1

  • PKNOX1 is expressed in many human tissues tested by Northern blot analysis [1].
  • After dissection, several pieces of the tissue were immediately immersed into the Sperm Prep Medium (Medi-Cult) and fixative (5.5% buffered glutaraldehyde) [18].
  • The high sensitivity (100%) and negative predictive rate (100%) in detecting HSIL in our study provide strong evidence that, instead of automatic referral to colposcopy, reflex HPV DNA testing may be used as an alternative triage method for women diagnosed with ASC-H on Thin Prep Pap test, especially for women older than 30 yr of age [13].

References

  1. Cloning of a novel homeobox-containing gene, PKNOX1, and mapping to human chromosome 21q22.3. Chen, H., Rossier, C., Nakamura, Y., Lynn, A., Chakravarti, A., Antonarakis, S.E. Genomics (1997) [Pubmed]
  2. Overexpression of PREP-1 in F9 teratocarcinoma cells leads to a functionally relevant increase of PBX-2 by preventing its degradation. Longobardi, E., Blasi, F. J. Biol. Chem. (2003) [Pubmed]
  3. The novel homeoprotein Prep1 modulates Pbx-Hox protein cooperativity. Berthelsen, J., Zappavigna, V., Ferretti, E., Mavilio, F., Blasi, F. EMBO J. (1998) [Pubmed]
  4. Prep1, a novel functional partner of Pbx proteins. Berthelsen, J., Zappavigna, V., Mavilio, F., Blasi, F. EMBO J. (1998) [Pubmed]
  5. MEIS C termini harbor transcriptional activation domains that respond to cell signaling. Huang, H., Rastegar, M., Bodner, C., Goh, S.L., Rambaldi, I., Featherstone, M. J. Biol. Chem. (2005) [Pubmed]
  6. Overexpression of FABP7 in Down syndrome fetal brains is associated with PKNOX1 gene-dosage imbalance. Sánchez-Font, M.F., Bosch-Comas, A., Gonzàlez-Duarte, R., Marfany, G. Nucleic Acids Res. (2003) [Pubmed]
  7. PREP1, MEIS1 homolog protein, regulates PF4 gene expression. Okada, Y., Matsuura, E., Nagai, R., Sato, T., Watanabe, A., Morita, I., Doi, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  8. Changing homeodomain residues 2 and 3 of Hoxa1 alters its activity in a cell-type and enhancer dependent manner. Remacle, S., Shaw-Jackson, C., Matis, C., Lampe, X., Picard, J., Rezsöhazy, R. Nucleic Acids Res. (2002) [Pubmed]
  9. The HOXC13-controlled expression of early hair keratin genes in the human hair follicle does not involve TALE proteins MEIS and PREP as cofactors. Jave-Suárez, L.F., Schweizer, J. Arch. Dermatol. Res. (2006) [Pubmed]
  10. Polymorphic variations in the expression of the chemical detoxifying UDP glucuronosyltransferases. Mackenzie, P.I., Gregory, P.A., Lewinsky, R.H., Yasmin, S.N., Height, T., McKinnon, R.A., Gardner-Stephen, D.A. Toxicol. Appl. Pharmacol. (2005) [Pubmed]
  11. Prospective, randomized, controlled comparison of the use of polyethylene glycol electrolyte lavage solution in four-liter versus two-liter volumes and pretreatment with either magnesium citrate or bisacodyl for colonoscopy preparation. Sharma, V.K., Chockalingham, S.K., Ugheoke, E.A., Kapur, A., Ling, P.H., Vasudeva, R., Howden, C.W. Gastrointest. Endosc. (1998) [Pubmed]
  12. Extraction of benzoylecgonine from urine specimens with Cerex Polycrom Clin II solid-phase extraction columns and the Speedisk Pressure Processor. Kuhnle, J.A., Churley, M., Kawasaki, S.Y., Lyons, T.P., Bruins, M.R. Journal of analytical toxicology. (2001) [Pubmed]
  13. Reflex high-risk human papilloma virus DNA test is useful in the triage of women with atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion. Wu, H.H., Allen, S.L., Kirkpatrick, J.L., Elsheikh, T.M. Diagn. Cytopathol. (2006) [Pubmed]
  14. Novel alternative PBX3 isoforms in leukemia cells with distinct interaction specificities. Milech, N., Kees, U.R., Watt, P.M. Genes Chromosomes Cancer (2001) [Pubmed]
  15. Cooperative interactions between PBX, PREP, and HOX proteins modulate the activity of the alpha 2(V) collagen (COL5A2) promoter. Penkov, D., Tanaka, S., Di Rocco, G., Berthelsen, J., Blasi, F., Ramirez, F. J. Biol. Chem. (2000) [Pubmed]
  16. Identification and characterization of human PKNOX2, a novel homeobox-containing gene. Imoto, I., Sonoda, I., Yuki, Y., Inazawa, J. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  17. The homeodomain Pbx2-Prep1 complex modulates hepatocyte nuclear factor 1alpha-mediated activation of the UDP-glucuronosyltransferase 2B17 gene. Gregory, P.A., Mackenzie, P.I. Mol. Pharmacol. (2002) [Pubmed]
  18. From testicular biopsy to human embryo. Jezek, D., Knezević, N., Kalanj-Bognar, S., Vukelić, Z., Krhen, I. Verhandlungen der Deutschen Gesellschaft für Pathologie. (2004) [Pubmed]
 
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