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 SOX9
Homo sapiens
 HIF1A
Homo sapiens
 Pax6
Mus musculus
 PAX6
Homo sapiens
 Snai2
Mus musculus
 PPARA
Homo sapiens
 Ppara
Mus musculus
 Thrb
Mus musculus
 SNAI2
Homo sapiens
 Tbr1
Mus musculus
Transcription Factor Encyclopedia  BETA
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Overview
No annotation is available in this section for this article. The content below is taken from a related TF, PBX1 (Homo sapiens).

PBX1 encodes the transcription factor PBX1 (Pre-B-Cell Leukemia Homeobox 1), a member of the three amino acid loop extension (TALE) family of homeodomain proteins that bind DNA and co-regulate gene transcription with HOX proteins. The PBX1 gene locus is mapped to 1q23.3 in humans (see Figure 1). PBX1 was originally identified as the gene fused to E2A as a result of the t(1;19) chromosomal translocation associated with pre-B cell leukemias[1]. Fusion with E2A (which contains two potent activation domains) converts PBX1 into an oncogenic transcriptional activator. Artificial promoters containing the ATCAATCAA consensus sequence are trans-activated by E2A-PBX1 but not PBX1 alone[2]. Thus the notion that E2A-PBX1 inappropriately trans-activates PBX1 target genes may be an important for leukemogenesis.

In humans, three genes related to PBX1 exist, namely PBX2, PBX3 (identified by low-stringency cDNA library screening [3]) and PBX4 (identified through database searching [4]). The protein products of these related genes have high sequence identity with the 266 residues flanking the homeodomain of PBX1 [3]. In contrast, the amino- and carboxy-termini are highly divergent (Figure 2). The human PBX1 gene consists of 9 exons and 8 introns. The intron-exon organization of the PBX1 gene is shown in Figure 3.

PBX1 functions as an essential mediator of development. PBX1-/- mice are late embryonic lethal[5][6] and as such, loss of function studies that use targeted knockouts have been especially informative. PBX1 has been considered a central co-regulator of organogenesis with roles in spleen, pancreas, kidney and adrenal development. Additionally, PBX1 is required for proximal limb[6] and axial skeleton development[7].

In the hematopoietic compartment, PBX1 governs the self renewal potential of hematopoietic stem cells by maintaining their quiescence[8]. Additionally, PBX1 serves to modulate early stages of B-cell development; PBX1 null embryonic stem (ES) cells fail to generate common lymphoid progenitor cells (CLPs), which results in a complete absence of B and natural killer (NK) cells[9].

Most recently, PBX1 was shown to be a direct transcriptional regulator of Nanog in human embryonic stem cells (hES cells)[10]. This combined with the observed importance for PBX1 in development and hematopoiesis suggests that PBX1 functions to maintain the pluripotentcy of hES cells [10].

In addition to its involvement in pre-B cell leukemia, PBX1 has also been indicated in ovarian cancers with high Notch3 copy number[11] and melanoma[12]. In ovarian cancer, Notch3 directly regulates the expression of PBX1, which is essential for cell proliferation and tumourigenicity[11]. In human A375 and 397 melanoma cell lines, PBX1 is highly expressed and siRNA knockdown of PBX1 expression results in growth suppression[12]. Together, these results suggest that PBX1 conveys a survival signal that is essential in multiple malignancies.

References
  1. Nourse J et al. Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell, 60(4):535-45. (PMID 1967982)
  2. Van Dijk MA et al. Pbx1 is converted into a transcriptional activator upon acquiring the N-terminal region of E2A in pre-B-cell acute lymphoblastoid leukemia. Proc. Natl. Acad. Sci. U.S.A., 90(13):6061-5. (PMID 8327485)
  3. Monica K et al. PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1. Mol. Cell. Biol., 11(12):6149-57. (PMID 1682799)
  4. Wagner K et al. Pbx4, a new Pbx family member on mouse chromosome 8, is expressed during spermatogenesis. Mech. Dev., 103(1-2):127-31. (PMID 11335119)
  5. Kim SK et al. Pbx1 inactivation disrupts pancreas development and in Ipf1-deficient mice promotes diabetes mellitus. Nat. Genet., 30(4):430-5. (PMID 11912494)
  6. Selleri L et al. Requirement for Pbx1 in skeletal patterning and programming chondrocyte proliferation and differentiation. Development, 128(18):3543-57. (PMID 11566859)
  1. Capellini TD et al. Pbx1/Pbx2 govern axial skeletal development by controlling Polycomb and Hox in mesoderm and Pax1/Pax9 in sclerotome. Dev. Biol., 321(2):500-14. (PMID 18691704)
  2. Ficara F et al. Pbx1 regulates self-renewal of long-term hematopoietic stem cells by maintaining their quiescence. Cell Stem Cell, 2(5):484-96. (PMID 18462698)
  3. Sanyal M et al. B-cell development fails in the absence of the Pbx1 proto-oncogene. Blood, 109(10):4191-9. (PMID 17244677)
  4. Chan KK et al. KLF4 and PBX1 Directly Regulate NANOG Expression in Human Embryonic Stem Cells. Stem Cells (PMID 19522013)
  5. Park JT et al. Identification of Pbx1, a potential oncogene, as a Notch3 target gene in ovarian cancer. Cancer Res., 68(21):8852-60. (PMID 18974129)
  6. Shiraishi K et al. Pre-B-cell leukemia transcription factor 1 is a major target of promyelocytic leukemia zinc-finger-mediated melanoma cell growth suppression. Oncogene, 26(3):339-48. (PMID 16862184)
Figures
No annotation is available in this section for this article. The content below is taken from a related TF, PBX1 (Homo sapiens).
FIGURE 1 Genomic map of PBX1.
Genomic map of the location of the PBX1 gene. Three different zooms are shown.
This figure is from NCBI's Map viewer images (http://www.ncbi.nlm.nih.gov/projects/mapview/map_search.cgi?taxid=9606).