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Gene Review

PBX1  -  pre-B-cell leukemia homeobox 1

Homo sapiens

Synonyms: Homeobox protein PBX1, Homeobox protein PRL, PRL, Pre-B-cell leukemia transcription factor 1
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Disease relevance of PBX1


Psychiatry related information on PBX1

  • Short-term administration of PRL and even long-term hyperprolactinemia in animals increases REM sleep [5].
  • Data were examined using the methodology described in the original report, consisting of averaging across individual nights PRL levels during REM and non-REM sleep stages as well as using a detailed spike by spike analysis of each individual pair of hormonal and sleep profiles [6].
  • A paradoxical rise in plasma PRL values was observed in anorexia nervosa patients during the course of a gonadotropin-releasing hormone infusion [7].
  • A sleep-onset rapid eye movement period occurred in all of the patients, and this abnormal phenomenon characteristic of narcolepsy was considered to be related to the suppression of GH release at the sleep onset and to the decrease of plasma PRL levels during the early part of sleep [8].
  • Plasma GH and PRL measurements in these four conditions revealed an effect of sleep deprivation independent of the presence or absence of melatonin [9].

High impact information on PBX1


Chemical compound and disease context of PBX1

  • Analysis of PBX1 as a candidate gene for type 2 diabetes mellitus in Pima Indians [14].
  • The foregoing disparity suggests the possibility of a role for estrogen in enhancing the effect of hypothyroidism on PRL release.(ABSTRACT TRUNCATED AT 400 WORDS)[15]
  • Plasma GH, PRL, and cortisol levels rose significantly in response to insulin-induced hypoglycemia [16].
  • The catecholamine dopamine (D) is involved in the regulation of LH and PRL secretion, whereas a dysregulated noradrenergic system may contribute significantly to symptoms encountered in affective disorders [17].
  • These data suggest that men with serum PRL levels above 50 ng/ml maintain a normal diurnal pattern of serum testosterone at a lower set point, and demonstrate hypogonadism with reduced urinary LH excretion and NPT [18].

Biological context of PBX1


Anatomical context of PBX1


Associations of PBX1 with chemical compounds

  • The human proto-oncogene PBX1 codes for a homeodomain containing protein that modulates expression of several genes, including those contributing to regulation of insulin action and glucose metabolism [14].
  • Comparison of the frequencies of the polymorphisms between affected and unaffected Pima Indians did not detect any significant differences, indicating that mutations in PBX1 do not explain the linkage of 1q with type 2 diabetes in this population [14].
  • We detected 16 single nucleotide polymorphisms in PBX1 including one causing a glycine to serine substitution at residue 21 [14].
  • Critical role for a single leucine residue in leukemia induction by E2A-PBX1 [25].
  • Enhanced autophagic cell death in expanded polyhistidine variants of HOXA1 reduces PBX1-coupled transcriptional activity and inhibits neuronal differentiation [26].

Physical interactions of PBX1


Regulatory relationships of PBX1

  • We find HoxA9-mediated CYBB-transcription requires Pbx1 but is inhibited by Meis1 [30].
  • We report here that experimental induction of E2a-Pbx1 enhances expression of BMI-1, a lymphoid oncogene whose product functions as a transcriptional repressor of the INK4A-ARF tumor suppressor locus [31].
  • The positive interaction between DAX1 and SF-1 in regulating PBX1 may be an important mechanism in this process [32].

Other interactions of PBX1

  • We map a site of interaction with HDAC1 to the PBX1 N terminus and show that the PBX partner is required for repression by the HOX-PBX complex [20].
  • However, PBX1 exogenously introduced into COL5A2-negative cells cannot stimulate FPB-driven transcription unless co-expressed with PREP1 [33].
  • Heterodimerization with PBX1 appears to be essential for nuclear localization of both PREP2 and PBX1 [34].
  • Cellular proliferation and transformation induced by HOXB4 and HOXB3 proteins involves cooperation with PBX1 [35].
  • Molecular studies showed E2A-PBX1 abnormalities in all examined cases (12 of 12) with the t(1;19), including the case lacking CD9 data [36].

Analytical, diagnostic and therapeutic context of PBX1


  1. The t(1;19)(q23;p13) results in consistent fusion of E2A and PBX1 coding sequences in acute lymphoblastic leukemias. Hunger, S.P., Galili, N., Carroll, A.J., Crist, W.M., Link, M.P., Cleary, M.L. Blood (1991) [Pubmed]
  2. Fusion with E2A converts the Pbx1 homeodomain protein into a constitutive transcriptional activator in human leukemias carrying the t(1;19) translocation. Lu, Q., Wright, D.D., Kamps, M.P. Mol. Cell. Biol. (1994) [Pubmed]
  3. Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice. Moskow, J.J., Bullrich, F., Huebner, K., Daar, I.O., Buchberg, A.M. Mol. Cell. Biol. (1995) [Pubmed]
  4. Fusion with E2A alters the transcriptional properties of the homeodomain protein PBX1 in t(1;19) leukemias. LeBrun, D.P., Cleary, M.L. Oncogene (1994) [Pubmed]
  5. Enhanced slow wave sleep in patients with prolactinoma. Frieboes, R.M., Murck, H., Stalla, G.K., Antonijevic, I.A., Steiger, A. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  6. The relationship between episodic variations of plasma prolactin and REM-non-REM cyclicity is an artifact. Van Cauter, E., Desir, D., Refetoff, S., Spire, J.P., Neol, P., H'Hermite, M., Robyn, C., Copinschi, G. J. Clin. Endocrinol. Metab. (1982) [Pubmed]
  7. Paradoxical prolactin response to gonadotropin-releasing hormone during weight gain in patients with anorexia nervosa. Beumont, P.J., Abraham, S.F., Turtle, J. J. Clin. Endocrinol. Metab. (1980) [Pubmed]
  8. Twenty-four-hour secretory patterns of growth hormone, prolactin, and cortisol in narcolepsy. Higuchi, T., Takahashi, Y., Takahashi, K., Niimi, Y., Miyasita, A. J. Clin. Endocrinol. Metab. (1979) [Pubmed]
  9. A model for the study of the acute effects of melatonin in man. Strassman, R.J., Peake, G.T., Qualls, C.R., Lisansky, E.J. J. Clin. Endocrinol. Metab. (1987) [Pubmed]
  10. FoxOs Are Lineage-Restricted Redundant Tumor Suppressors and Regulate Endothelial Cell Homeostasis. Paik, J.H., Kollipara, R., Chu, G., Ji, H., Xiao, Y., Ding, Z., Miao, L., Tothova, Z., Horner, J.W., Carrasco, D.R., Jiang, S., Gilliland, D.G., Chin, L., Wong, W.H., Castrillon, D.H., Depinho, R.A. Cell (2007) [Pubmed]
  11. Chimeric homeobox gene E2A-PBX1 induces proliferation, apoptosis, and malignant lymphomas in transgenic mice. Dedera, D.A., Waller, E.K., LeBrun, D.P., Sen-Majumdar, A., Stevens, M.E., Barsh, G.S., Cleary, M.L. Cell (1993) [Pubmed]
  12. extradenticle, a regulator of homeotic gene activity, is a homolog of the homeobox-containing human proto-oncogene pbx1. Rauskolb, C., Peifer, M., Wieschaus, E. Cell (1993) [Pubmed]
  13. The human t(1;19) translocation in pre-B ALL produces multiple nuclear E2A-Pbx1 fusion proteins with differing transforming potentials. Kamps, M.P., Look, A.T., Baltimore, D. Genes Dev. (1991) [Pubmed]
  14. Analysis of PBX1 as a candidate gene for type 2 diabetes mellitus in Pima Indians. Thameem, F., Wolford, J.K., Bogardus, C., Prochazka, M. Biochim. Biophys. Acta (2001) [Pubmed]
  15. Robustness of the male lactotropic axis to the hyperprolactinemic stimulus of primary thyroidal failure. Iranmanesh, A., Lizarralde, G., Veldhuis, J.D. J. Clin. Endocrinol. Metab. (1992) [Pubmed]
  16. Failure of naloxone to influence plasma growth hormone, prolactin, and cortisol secretions induced by insulin hypoglycemia. Wakabayashi, I., Demura, R., Miki, N., Ohmura, E., Miyoshi, H., Shizume, K. J. Clin. Endocrinol. Metab. (1980) [Pubmed]
  17. Inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates nocturnal melatonin secretion in humans. Zimmermann, R.C., Krahn, L., Klee, G., Delgado, P., Ory, S.J., Lin, S.C. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  18. Return of gonadal function in men with prolactin-secreting pituitary tumors. Murray, F.T., Cameron, D.F., Ketchum, C. J. Clin. Endocrinol. Metab. (1984) [Pubmed]
  19. PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1. Monica, K., Galili, N., Nourse, J., Saltman, D., Cleary, M.L. Mol. Cell. Biol. (1991) [Pubmed]
  20. Cell signaling switches HOX-PBX complexes from repressors to activators of transcription mediated by histone deacetylases and histone acetyltransferases. Saleh, M., Rambaldi, I., Yang, X.J., Featherstone, M.S. Mol. Cell. Biol. (2000) [Pubmed]
  21. The recruitment of SOX/OCT complexes and the differential activity of HOXA1 and HOXB1 modulate the Hoxb1 auto-regulatory enhancer function. Di Rocco, G., Gavalas, A., Popperl, H., Krumlauf, R., Mavilio, F., Zappavigna, V. J. Biol. Chem. (2001) [Pubmed]
  22. Different molecular consequences of the 1;19 chromosomal translocation in childhood B-cell precursor acute lymphoblastic leukemia. Privitera, E., Kamps, M.P., Hayashi, Y., Inaba, T., Shapiro, L.H., Raimondi, S.C., Behm, F., Hendershot, L., Carroll, A.J., Baltimore, D. Blood (1992) [Pubmed]
  23. Site-specific translocation and evidence of postnatal origin of the t(1;19) E2A-PBX1 fusion in childhood acute lymphoblastic leukemia. Wiemels, J.L., Leonard, B.C., Wang, Y., Segal, M.R., Hunger, S.P., Smith, M.T., Crouse, V., Ma, X., Buffler, P.A., Pine, S.R. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  24. PBX1 intracellular localization is independent of MEIS1 in epithelial cells of the developing female genital tract. Dintilhac, A., Bihan, R., Guerrier, D., Deschamps, S., Bougerie, H., Watrin, T., Bonnec, G., Pellerin, I. Int. J. Dev. Biol. (2005) [Pubmed]
  25. Critical role for a single leucine residue in leukemia induction by E2A-PBX1. Bayly, R., Murase, T., Hyndman, B.D., Savage, R., Nurmohamed, S., Munro, K., Casselman, R., Smith, S.P., LeBrun, D.P. Mol. Cell. Biol. (2006) [Pubmed]
  26. Enhanced autophagic cell death in expanded polyhistidine variants of HOXA1 reduces PBX1-coupled transcriptional activity and inhibits neuronal differentiation. Paraguison, R.C., Higaki, K., Yamamoto, K., Matsumoto, H., Sasaki, T., Kato, N., Nanba, E. J. Neurosci. Res. (2007) [Pubmed]
  27. HOXB6 overexpression in murine bone marrow immortalizes a myelomonocytic precursor in vitro and causes hematopoietic stem cell expansion and acute myeloid leukemia in vivo. Fischbach, N.A., Rozenfeld, S., Shen, W., Fong, S., Chrobak, D., Ginzinger, D., Kogan, S.C., Radhakrishnan, A., Le Beau, M.M., Largman, C., Lawrence, H.J. Blood (2005) [Pubmed]
  28. Oncogenic homeodomain transcription factor E2A-Pbx1 activates a novel WNT gene in pre-B acute lymphoblastoid leukemia. McWhirter, J.R., Neuteboom, S.T., Wancewicz, E.V., Monia, B.P., Downing, J.R., Murre, C. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  29. Evaluation of sequence variants in the pre-B cell leukemia transcription factor 1 gene: a positional and functional candidate for type 2 diabetes and impaired insulin secretion. Wang, H., Chu, W., Wang, X., Zhang, Z., Elbein, S.C. Mol. Genet. Metab. (2005) [Pubmed]
  30. HOXA9 activates transcription of the gene encoding gp91Phox during myeloid differentiation. Bei, L., Lu, Y., Eklund, E.A. J. Biol. Chem. (2005) [Pubmed]
  31. Bmi-1 regulation of INK4A-ARF is a downstream requirement for transformation of hematopoietic progenitors by E2a-Pbx1. Smith, K.S., Chanda, S.K., Lingbeek, M., Ross, D.T., Botstein, D., van Lohuizen, M., Cleary, M.L. Mol. Cell (2003) [Pubmed]
  32. CBP/p300-interacting transactivator, with Glu/Asp-rich C-terminal domain, 2, and pre-B-cell leukemia transcription factor 1 in human adrenal development and disease. Ferraz-de-Souza, B., Martin, F., Mallet, D., Hudson-Davies, R.E., Cogram, P., Lin, L., Gerrelli, D., Beuschlein, F., Morel, Y., Huebner, A., Achermann, J.C. J. Clin. Endocrinol. Metab. (2009) [Pubmed]
  33. 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]
  34. Characterization of PREP2, a paralog of PREP1, which defines a novel sub-family of the MEINOX TALE homeodomain transcription factors. Fognani, C., Kilstrup-Nielsen, C., Berthelsen, J., Ferretti, E., Zappavigna, V., Blasi, F. Nucleic Acids Res. (2002) [Pubmed]
  35. Cellular proliferation and transformation induced by HOXB4 and HOXB3 proteins involves cooperation with PBX1. Krosl, J., Baban, S., Krosl, G., Rozenfeld, S., Largman, C., Sauvageau, G. Oncogene (1998) [Pubmed]
  36. Predictability of the t(1;19)(q23;p13) from surface antigen phenotype: implications for screening cases of childhood acute lymphoblastic leukemia for molecular analysis: a Pediatric Oncology Group study. Borowitz, M.J., Hunger, S.P., Carroll, A.J., Shuster, J.J., Pullen, D.J., Steuber, C.P., Cleary, M.L. Blood (1993) [Pubmed]
  37. Unexpected heterogeneity in E2A/PBX1 fusion messenger RNA detected by the polymerase chain reaction in pediatric patients with acute lymphoblastic leukemia. Izraeli, S., Kovar, H., Gadner, H., Lion, T. Blood (1992) [Pubmed]
  38. E2A-PBX1 chimeric transcript status at end of consolidation is not predictive of treatment outcome in childhood acute lymphoblastic leukemias with a t(1;19)(q23;p13): a Pediatric Oncology Group study. Hunger, S.P., Fall, M.Z., Camitta, B.M., Carroll, A.J., Link, M.P., Lauer, S.J., Mahoney, D.H., Pullen, D.J., Shuster, J.J., Steuber, C.P., Cleary, M.L. Blood (1998) [Pubmed]
  39. Establishment of a new human pre-B acute lymphoblastic leukemia cell line (KMO-90) with 1;19 translocation carrying p53 gene alterations. Sotomatsu, M., Hayashi, Y., Kawamura, M., Yugami, S., Shitara, T. Leukemia (1993) [Pubmed]
  40. Correlation of cytoplasmic Ig mu (C mu) and E2A-PBX1 fusion transcripts in t(1;19) B lineage ALL: discrepancy in C mu detection by slide immunofluorescence and flow cytometry. Troussard, X., Valensi, F., Salomon-Nguyen, F., Debert, C., Flandrin, G., MacIntyre, E. Leukemia (1995) [Pubmed]
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