Disease relevance of POU2F2

• Oct-2, therefore, acts as a cell survival factor in t(14;18) lymphoma cells by directly activating the antiapoptotic gene bcl-2 [1].
• A fragment of Oct-2 containing POUHD and an adjoining linker was expressed in Escherichia coli and characterized by three-dimensional nuclear magnetic resonance (3D-NMR) spectroscopy [2].
• To analyze the various Oct2 isoforms, they were overexpressed in HeLa cells using recombinant vaccinia virus [3].
• In this study, the mRNA levels of the organic ion transporters were quantified by real-time PCR in normal parts of renal tissues from seven nephrectomized patients with renal cell carcinoma, and the distributions and localization of human (h)OAT1, hOAT3, and hOCT2 proteins were investigated by immunohistochemical analyses in the human kidney [4].
• Lower Prevalence of the OCT2 Ser270 Allele in Patients with Essential Hypertension* [5].

High impact information on POU2F2

• Although these two elements have no sequence similarity, they are both recognized in vitro by the ubiquitous octamer transcription factor OTF-1 (reviewed refs 13 and 14) and the lymphoid-specific OTF-2 (reviewed in refs 15 and 16) [6].
• Oct-2 also possesses a potential 'leucine zipper' domain, where four leucines are each separated by exactly seven residues [7].
• The DNA-binding domain of Oct-2 is structurally related to the homeo box consensus and thus contains a potential helix-turn-helix sequence [7].
• Octamer factor 2 (Oct-2, OTF-2, NF-A2) is an 'upstream' promoter factor that binds to the octamer motif (ATGCAAAT) implicated in control of immunoglobulin gene transcription in B-lymphocytes [8].
• Many studies indicate that the cell type-specific transcription factor OTF-2 plays a central role in the lymphoid-specific transcription of immunoglobulin genes [9].

Chemical compound and disease context of POU2F2

• These findings demonstrate that uptake of cis-platin is mediated by hOCT2 in renal proximal tubules, explaining its organ-specific toxicity [10].
• A hypothetical three-dimensional structure of OCT2 based on a homology model that used the Escherichia coli glycerol 3-phosphate transporter as a template has been described (Zhang, X., Shirahatti, N. V., Mahadevan, D., and Wright, S. H. (2005) J. Biol. Chem. 280, 34813-34822) [11].

Biological context of POU2F2

• The genes encoding for these three respective transcription factors have been mapped at 11p11.2 (SPI1), 11q23.1 (POU2AF1), and 19q13.2 (POU2F2); these are chromosomes recurrently affected in HL [12].
• The functional changes of hOCT2 variants were evaluated in vitro, and those genetic polymorphisms of hOCTs were compared among different ethnic populations [13].
• From direct DNA sequencing, 7 of 13 coding variants were nonsynonymous single-nucleotide polymorphisms (SNPs), including four variants from hOCT1 (F160L, P283L, P341L, and M408V) and three from hOCT2 (T199I, T201M, and A270S), whereas 6 were synonymous SNPs [13].
• This conclusion is supported by the finding that transfection of HEK293 cells with cDNA encoding either hOCT1, hOCT2, or hOCT3 did not enhance specific [(14)C]agmatine accumulation compared to nontransfected cells [14].
• In addition, human hs4 enhancer activity required Oct-2 and correlated with expression of Oct coactivator from B cells (OCA-B) [15].

Anatomical context of POU2F2

• Co-transfection of human TBP and Oct2 expression vectors into B cells resulted in a synergistic activation of an octamer motif containing promoter [16].
• Gene-targeting studies showed that Oct-1 and Oct-2 are largely dispensable for B-cell development and immunoglobulin production, although both Oct-2 and Bob-1 are required for a proper immune response and germinal center formation [1].
• Furthermore, Oct-1 in combination with co-regulator Bob.1, or Oct-2 alone, could drive transcription of a heterologous thymidine kinase promoter linked to the FR in both B cells and epithelial cells [17].
• While Oct-1 is ubiquitous, Oct-2 is predominantly expressed in B cells, in activated T cells and in nervous system [18].
• In other cell types however, all three isoforms activate the involucrin promoter and this effect is also observed at low concentrations of Oct-2 in keratinocytes [19].

Associations of POU2F2 with chemical compounds

• The different alternatively spliced isoforms of the Oct-2 transcription factor repress the involucrin promoter in a cell type-specific manner [19].
• The activation required binding of OTF-1/OTF-2, and C4 could not stimulate transcription by itself, implying a synergistic interaction [20].
• Sarkosyl inhibition studies suggest that both Oct1 and Oct2 function in vitro by stabilizing preinitiation complexes without affecting the reinitiation rate of RNA polymerase II [3].
• The Organic Cation Transporter 2, OCT2 (SLC22A2), has been implicated in renal dopamine handling as well as in the inactivation of circulating catecholamines and is supposed to be involved in blood pressure regulation [5].
• However, oxaliplatin showed almost no influence on the TEA uptakes in the HEK293 cells expressing hOCT1, hOCT2, and hOCT3 [21].

Physical interactions of POU2F2

• We show that both affinity-purified OTF-1 and OTF-2 bind to the TAATGARAT sequence and that Vmw65 induces the formation of an additional complex that involves OTF-1 and that is further retarded in a band-shift gel assay [22].
• The B-lymphocyte-specific activity of the immunoglobulin mu heavy-chain gene enhancer has been attributed to the octamer motif (ATTTGCAT) present within the enhancer that binds a B-cell-specific factor designated NF-A2/OTF-2 [23].

Regulatory relationships of POU2F2

• Oct2 can stimulate transcription in B-cell nuclear extracts and in HeLa nuclear extracts depleted of the ubiquitous factor Oct1 by wheat germ lectin affinity chromatography [3].

Other interactions of POU2F2

• We had previously shown that the ubiquitous Oct1 and the lymphoid-specific Oct2 transcription factors stimulate transcription at the level of stable preinitiation complex formation [16].
• We show that the POU homeodomain of Oct2 and the evolutionarily conserved C-terminal core domain of TBP are both required and sufficient for the interaction [16].
• An NMR model is obtained from Oct-2, a human B-cell specific transcription factor which participates in the regulation of immunoglobulin genes [2].
• In transfected mammalian cells, a transcriptionally inert wild-type but not an L501P GR peptide potentiated transcriptional activation by Oct-2 100-fold above the level that could be attained in the cell by expressing Oct-2 alone [24].
• However, the stimulatory effect was not specific to FMBP-1, BYB also enhancing the binding of mammalian transcription factors OTF2, SP1 and AP2 to their specific binding elements [25].

Analytical, diagnostic and therapeutic context of POU2F2

• Although these regions did not contain canonical octamer motifs, we observed the direct interaction of Oct-2 with all three sites both in vitro by EMSA and in vivo by chromatin immunoprecipitation assay [1].
• Physical binding to the FR by the cellular transcription factors Oct-1 and Oct-2 was demonstrated by using an electrophoretic mobility-shift assay [17].
• Both statins increased Oct-1 and Oct-2 nuclear protein levels (Western blot) [26].
• The B cell-specific nuclear factor OTF-2 positively regulates transcription of the human class II transplantation gene, DRA [27].
• This study investigated the association of the OCT2 Ala270Ser polymorphism with essential hypertension and its impact on blood pressure status in 607 Caucasian patients who underwent left heart catheterization [5].

References