Disease relevance of NONO

• 55 kDa nuclear matrix protein (nmt55) mRNA is expressed in human prostate cancer tissue and is associated with the androgen receptor [1].
• Here, we show that the INS region in HIV-1 gag mRNA is a high-affinity ligand of p54nrb/PSF, a heterodimeric transcription/splicing factor [2].
• AFX1 and p54nrb: fine mapping, genomic structure, and exclusion as candidate genes of X-linked dystonia parkinsonism [3].
• We have identified and characterized a 55 kDa nuclear protein (referred to as nmt55) from human breast tumors and MCF-7, human adenocarcinoma breast cell line, using site-directed monoclonal antibodies [4].
• Synthetic nono- and bifunctional alpha-methylene lactone derivatives including deoxyvernolepin and kihydrodeoxyvernolepin were tested as inhibitors of the growth of CCRF-CEM human lymphoblastic leukemia cells in culture [5].

High impact information on NONO

• Here we show that the major interacting-proteins with DJ-1 in dopaminergic neuronal cells are the nuclear proteins p54nrb and pyrimidine tract-binding protein-associated splicing factor (PSF), two multifunctional regulators of transcription and RNA metabolism [6].
• Thus, DJ-1 is a neuroprotective transcriptional co-activator that may act in concert with p54nrb and PSF to regulate the expression of a neuroprotective genetic program [6].
• Both DJ-1 and p54nrb block oxidative stress and mutant alpha-synuclein-induced cell death [6].
• Both subunits contained nuclear export and nuclear retention signals, whereas p54nrb was continuously exported from the nucleus and associated with INS-containing mRNA in the cytoplasm, suggesting its additional role at late steps of mRNA metabolism [2].
• Thus, the lack of activity of p54nrb in F9 cells is due to an ineffective DNA-binding domain [7].

Biological context of NONO

• 2. In addition we define an X chromosome inversion inv(X)(p11.2;q12) that results in the fusion of the NonO (p54nrb) gene to TFE3 [8].
• NonO (p54nrb), the human homologue of the Drosophila gene NonAdiss which controls the male courtship song, is closely related to PSF and also believed to be involved in RNA splicing [8].
• We identified a specific upregulated gene encoding a 55 kDa nuclear matrix protein (nmt55) in human prostate cancer. nmt55 gene expression in human prostate cancer tissue was higher (20/26 cases) than that in normal prostate tissue [1].
• Mechanism of interferon action. II. Induction and decay kinetics of the antiviral state and protein P54 in human amnion U cells treated with gamma interferon [9].
• AFX1 and p54nrb were excluded as candidates of DYT3 by sequencing of the exons and the flanking intronic sequences in an XDP patient and a control, and by Northern blot analysis [3].

Anatomical context of NONO

• Two proteins present in HeLa cell extract, the splicing and transcription-associated factors, PSF and p54nrb/NonO, bound specifically and could be purified to virtual homogeneity by chromatography on immobilized CTD matrices [10].
• Incubation with NONO induced cell damage in control lymphocytes but did not further damage the already affected untreated SALS lymphocytes [11].
• By immunoblot inhibition and subcellular (cytosolic, nuclear) cell fractionation we identified a 55 kDa nuclear autoantigen expressed in intestinal, endothelial cells and in fibroblasts which was recognized by IgA antibodies of approximately half of the celiac disease patients and cross-reacted with wheat proteins [12].
• The development of the acoustics of the auditory periphery of the ferret was examined by measuring the spectral transfer functions (STFs) and the directional characteristics of the outer ears of animals ranging in age from postnatal day 32 (P32) to P54 [13].
• Changes in the mRNA levels of Jurkat T cells induced by cell-cell contact with adherent cells were also found for M-type pyruvate kinase, for tropomyosin TM30 and for the p54nrb gene product [14].

Associations of NONO with chemical compounds

• In this study, we investigated the effect of the NO-releasing agent, diethylamine NONOate (NONO), on lymphocytes from patients affected by the sporadic form of ALS (SALS) and controls by flow cytometry [11].
• In addition, site-directed mutagenesis indicated that the interaction of Pin1 with p54nrb was mediated by three threonine residues located in the proline-rich carboxy-terminal extremity of the protein [15].
• While the biological action of these molecules are thought to be primarily mediated by ca. 55 kDa nuclear retinoic acid receptors, a number of structurally similar 15-20 kDa proteins are involved in the transport, and possibly metabolism, of these compounds [16].
• Also, the synthesis of 55-kDa nuclear protein(s) was stimulated throughout the cell cycle in the presence of 3 mM caffeine [17].
• Coordinate regulation of the proximal and distal steps of the pathway of purine synthesis de nono in WI-L2 human lymphoblasts [18].

Physical interactions of NONO

• Here we show that PSF interacts with p54nrb, a highly related protein first identified based on cross-reactivity to antibodies against the yeast second-step splicing factor Prpl8 [19].
• We show that PSP1 interacts in vivo with a subset of the total cellular pool of p54nrb [20].

Regulatory relationships of NONO

• The PSA promoter was activated by nmt55 expression [1].
• The incubation with NONO induced a time-dependent decrease of Bcl-2 and SOD1 in control lymphocytes [11].

Other interactions of NONO

• These results suggest the possibility that nmt55 expression is related to hormone-dependency or -independence associated with the AR [1].
• Loss of expression of a 55 kDa nuclear protein (nmt55) in estrogen receptor-negative human breast cancer [4].
• Thus paraspeckles are the sites where a subset of the total cellular pool of p54nrb is targeted in a RNA Polymerase II-dependent manner [20].
• AFX1 is flanked by loci DXS7116 and Il2R gamma, and p54nrb by loci DXS6673E and DXS7120 [3].

Analytical, diagnostic and therapeutic context of NONO

• We purified this polypeptide from HeLa cells using a Western blot assay, and named it p54nrb (for nuclear RNA-binding protein, 54 kDa). cDNAs encoding p54nrb were cloned with probes derived from partial sequence of the purified protein [21].
• Chromosomal mapping, using fluorescent in situ hybridization (FISH), located nmt55 gene to the X chromosome, region q13 [4].
• Roux-en-Y gastric bypass (RYGBP) was performed on 244 patients who were compared with 187 patients who did not undergo surgery (NonOP) [22].
• One hundred twenty-eight patients (61%) were managed nonoperatively (Nonop), whereas 83 (39%) were managed with craniotomy [operatively (Op)] [23].
• Immunoblotting analysis identified localized antigens during different phases of the cell cycle, including a 68/71 kDa cytoplasmic protein and a 55 kDa nuclear protein in interphase, and a 55/70 kDa protein in mitosis [24].

References