Disease relevance of PBX2

• In addition, we applied a competitive selection procedure to target phage antibodies to the desired portion of a recombinant fusion protein and to select phage antibodies capable of discriminating between the two highly homologous homeobox proteins PBX1a and PBX2 [1].
• PBX proteins are highly expressed in HOX11 immortalized/transformed hematopoietic cells; in particular, the 10q24 translocation-carrying T-ALL Sil and K3P lines were found to selectively express PBX2 [2].
• Overexpression of PREP-1 in F9 teratocarcinoma cells leads to a functionally relevant increase of PBX-2 by preventing its degradation [3].
• DNA sequence analysis of 5.5 kb of DNA corresponding to the G17 gene has revealed that it encodes PBX2, a homeodomain-containing protein with extensive similarity to PBX1 (which is involved in t(1;19) chromosomal translocations in acute pre-B-cell leukemias) [4].
• AIM: To explore the effect of gastrin 17 (G17) on beta-catenin/T cell factor-4 (Tcf-4) signaling in colonic cancer cell line Colo320WT [5].

High impact information on PBX2

• By performing Western blottings and supershift assays, the binding proteins were identified as homeodomain proteins, MEIS1, PBX1B, and PBX2 [6].
• HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells [7].
• Here we demonstrate that the homeodomains encoded by PBX1, as well as by the highly related PBX2 and PBX3 genes, bind the DNA sequence ATCAATCAA [8].
• Similar to PBX1 RNA, PBX3 RNA is alternatively spliced to yield two translation products with different carboxy termini, a feature not observed for PBX2 [9].
• We show that overexpression of PREP-1 influences the level of PBX-2 protein maintaining the PREP-1-PBX balance [3].

Biological context of PBX2

• Thus, these studies demonstrate that the homeodomain proteins, MEIS1, PBX1B, and PBX2, play an important role in megakaryocytic gene expression [6].
• The PBX2 gene was originally localized only to human chromosome 3q22-q23 [4].
• Further PCR analysis of the genes and reverse transcribed mRNA from the hybrid cell lines has revealed that the copies of the PBX2 gene on human chromosomes 6 and 1 are expressed, while the copy on human chromosome 3 may be a processed pseudogene [4].
• Three genes in the human MHC class III region near the junction with the class II: gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3 [10].
• The novel gene G17, located in the human major histocompatibility complex, encodes PBX2, a homeodomain-containing protein [4].

Anatomical context of PBX2

• Expression of PBX2 or PBX3 was not restricted to particular states of differentiation or development, as mRNA transcripts of these genes were detected in most fetal and adult tissues and all cell lines, unlike PBX1, which is not expressed in lymphoid cell lines [9].
• First, a PBX2 Regulatory Element PRE-1048 has been identified which contains a novel DNA-binding sequence and mediates significant activation of the HOX11 gene in K562 cells [11].
• We were unable to stain the small type G4, the medium-sized types G8 and G9, and the large cell types G17 and G18: this suggests that they might not project to the superficial layers of the dorsolateral optic tectum, at least, in the turtle [12].
• Negative regulators include the Pre B cell homeobox factor (Pbx2) and its dimerization partner, Pbx regulating protein 1 (Prep1) [13].
• Immunocytochemistry showed that beta-catenin was translocated from the cell membranes into the cytoplasm and nucleus under G17 treatment [5].

Associations of PBX2 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 [3].
• Expression levels of beta-catenin in a TX-100 soluble fraction and TX-100 insoluble fraction of Colo320WT cells treated with G17 were detected by co-immuniprecipation and Western blot [5].
• These include factors such as Hepatocyte Nuclear Factor 1, CAAT-Enhancer Binding Protein, Octamer transcription Factor 1 and Pbx2, which appear to control the constitutive levels of UGTs in tissues and organs [14].

Regulatory relationships of PBX2

• This is the first report of a homeobox gene being specifically regulated by PBX2 and the second report of a vertebrate homeobox target gene of a PBX protein [11].

Other interactions of PBX2

• In myeloid cells, HOXA9, MEIS1, and PBX2 are all strongly expressed in the nucleus, where a portion of their signals are colocalized within nuclear speckles [7].
• A complex containing PBX2 contributes to activation of the proto-oncogene HOX11 [11].
• The glandular expression of HOXA10 and Meis1 was menstrual cycle stage specific, whereas glandular Pbx2 expression did not vary [15].
• Hence, dimerization with PREP-1 appears to decrease proteasomal degradation of PBX-2 [3].
• In contrast, the corresponding Co(II)-desferal conjugate directed the cleavage specific to only G sites (G12, G16, G17 and G19) [16].

References