Disease relevance of PURA

• Deletions of PURA, at 5q31, and PURB, at 7p13, in myelodysplastic syndrome and progression to acute myelogenous leukemia [1].
• The gene encoding Puralpha has been localized to a human locus which is frequently deleted in myelogenous leukemias and other cancers and Puralpha gene deletions have been detected in many cases of lymphoid cancers [2].
• In two-thirds of the 16 cadavers the AURA, PURA and RRA showed direct communication with the corresponding collateral arteries; the IRA exhibited less well-defined communication in 15 of the cadavers [3].
• Here we have examined the structural and functional interaction between two cellular regulatory proteins, YB-1 and Puralpha, on the 23-bp sequence element derived from the enhancer-promoter of the human polyomavirus JCV [4].
• Previous work has shown that the Tat protein, encoded by human immunodeficiency virus type 1 (HIV-1), can interact with cellular protein Puralpha to enhance both TAR-dependent HIV-1 transcription and JCV late gene transcription [5].

High impact information on PURA

• A 10-nucleotide GC-rich consensus sequence identified in RNAs associated with Puralpha derived from human U-87MG cells plays an important role in the Puralpha:Tat interaction as examined by an in vitro reconstitution assay [6].
• By using JCV as a model, we investigated the role of the viral early protein tumor antigen (TAg) in the binding of two cellular proteins, Pura alpha and YB-1, to JCV regulatory sequences [7].
• Ectopic expression of Puralpha and Purbeta decreased betaMyHC reporter gene expression, while mutation of the dbetaNRE-S element increased expression in C2C12 myotubes [8].
• Affinity chromatography and coimmunoprecipitation provide evidence for a direct interaction between Puralpha and YB-1 in the absence of the DNA sequence [4].
• Reciprocal interaction between two cellular proteins, Puralpha and YB-1, modulates transcriptional activity of JCVCY in glial cells [4].

Biological context of PURA

• In this study two genes, PURA and PURB, encoding functionally cooperative proteins in the Pur family, are localized to chromosome bands 5q31.1 and 7p13, respectively [1].
• We have localized the Pur alpha gene (PURA) to human chromosome band 5q31 by fluorescence in situ hybridization with a 16-kb genomic probe together with hybridization of a cDNA probe to blots of DNA from human-hamster cell lines containing individual human chromosomes [9].
• Double chromatin immunoprecipitation using antibodies to Cdk2 and Puralpha reveals that both proteins colocalize in HeLa cells to DNA segments upstream of the c-MYC gene [10].
• The RNA species disrupted Pura/E2F-1 interaction and affected cell growth [11].
• CONCLUSION: E2F-1/Pura interaction has a role in the control of cell proliferation [11].

Anatomical context of PURA

• During PMA-induced differentiation, the ability of Puralpha to activate the CD11c promoter in U937 cells increases, as does that of Sp1 [12].
• Puralpha is a ubiquitous, sequence-specific DNA- and RNA-binding protein which is highly conserved in eukaryotic cells [2].
• Ectopic expression of YB-1 and Puralpha in glial cells synergistically stimulated viral promoter activity via the 23-bp sequence element [4].
• Previously, we have reported that this protein controls BC1 RNA expression and its subsequent distribution within dendrites and that Puralpha is associated with polyribosomes [13].
• Overexpression of YB-1 and Puralpha in Jurkat cells was shown to reduce the level of cell surface Fas staining, providing further evidence that these proteins regulate the fas promoter [14].

Associations of PURA with chemical compounds

• In this study, we demonstrate that Puralpha and Purbeta interact with each other via highly specific protein-protein interactions and bind to the purine-rich strand of the MCAT enhancer in the form of both homo- and heteromeric complexes [15].
• Long-term treatment (>4 hours) with aldosterone induced the mRNA expression of pparalpha and puralpha [16].
• Through in vitro studies with bacterially expressed glutathione S-transferase fusion proteins, and the synthetic peptides corresponding to various central regions of Puralpha, the domain which is important for the self-association of Puralpha is localized to acidic leucine-rich repeats [17].
• Protein phosphorylation visualized by Pro-Q Diamond fluorescent staining showed that neurofilament light polypeptide, glial fibrillary acidic protein, heat shock protein 8 and transcriptional activator protein pur-alpha were more intensely phosphorylated with exercise as compared with sedentary control levels [18].
• The microglial cell-line, BV-2, was either cultured on poly-d-lysine coated dishes (2D culture conditions) or in a BD Pura Matrix Peptide Hydrogel (3D culture conditions) in the absence or presence of the extracellular matrix proteins, fibronectin and collagen type I, respectively [19].

Physical interactions of PURA

• Previously, the multifunctional Pura protein was found to bind to E2F-1 and inhibit E2F-1 transcriptional activity [11].
• In this study, we report that in U937 cells, expression of the CD11c gene is mediated by the ssDNA-binding protein Puralpha [12].

Regulatory relationships of PURA

• Electrophoretic mobility shift assays performed with and without RNase treatment demonstrate that RNA inhibits the interaction between Puralpha and its target DNA sequence [17].
• Puralpha activates PDGF-A gene transcription via interactions with a G-rich, single-stranded region of the promoter [20].

Other interactions of PURA

• Frequency of PURA deletion and segregation with EGR-1 indicate that PURA is within the most commonly deleted segment in myeloid disorders characterized by del(5)(q31) [1].
• Localization of PURA, the gene encoding the sequence-specific single-stranded-DNA-binding protein Pur alpha, to chromosome band 5q31 [9].
• One of these proteins is identical to Puralpha, a retinoblastoma-binding protein previously implicated in both transcriptional activation and DNA replication [21].
• One of these elements, a CT box, interacts with the regulatory factors heterogeneous nuclear ribonucleoprotein K and Puralpha [22].
• Puralpha of 28 kDa was previously identified as a replication-origin-binding protein that is ubiquitously expressed in proliferating cells [23].

Analytical, diagnostic and therapeutic context of PURA

• Moreover, microinjection studies demonstrate that Puralpha causes either a G(1) or G(2) arrest depending on the cell cycle time of injection [2].
• In this paper the vascular anatomy of recurrent flaps of the upper arm is described, based on dissections of 16 cadavers, in which the anterior ulnar recurrent (AURA), posterior ulnar recurrent (PURA), radial recurrent (RRA) and interosseous recurrent (IRA) arteries were dissected [3].
• Characterization of the mouse Puralpha gene by restriction analysis/Southern blotting and sequencing revealed that the Puralpha gene contains only one intron within the 5' UTR and the open reading frame was intact [24].
• Interestingly, results from cell culture studies revealed that incubation of oligodendrocytes with JCV led to a drastic decrease in the level of MEF-1/Puralpha protein [25].
• Using mouse brain, double-RNA immunoprecipitation places Puralpha together with Staufen or FMRP on BC1 RNA and specific mRNA species in vivo [26].

References