Disease relevance of EXOSC9

• PM-Scl-75 is the main autoantigen in patients with the polymyositis/scleroderma overlap syndrome [1].
• This is reflected in wider IgE reactivity to individual timothy pollen allergens in Finnish Karelia, including the major allergen Phl p 5, and increased pollen allergy [2].
• Solution structure of the human immunodeficiency virus type 1 p6 protein [3].
• Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease inhibitors have been shown to contain a mutation in the p1/p6 Gag precursor cleavage site [4].
• Interaction with the p6 domain of the gag precursor mediates incorporation into virions of Vpr and Vpx proteins from primate lentiviruses [5].

High impact information on EXOSC9

• Immunoblot analysis of proteins with allergen-specific antibodies did not detect Lol p 5 in the transgenic pollen [6].
• Therefore, it can be expected that down-regulation of Lol p 5 production can significantly reduce the allergic potential of ryegrass pollen [6].
• The transgenic ryegrass plants in which Lol p 5 gene expression is perturbed showed normal fertile pollen development, indicating that genetic engineering of hypoallergenic grass plants is possible [6].
• In addition, we identified a significant number of patients who had anti-PM-Scl-75 but not anti-PM-Scl-100 antibodies [1].
• The polymyositis-scleroderma autoantigen interacts with the helix-loop-helix proteins E12 and E47 [7].

Chemical compound and disease context of EXOSC9

• These anti-gag antibodies mapped to linear B-cell epitopes within the matrix (MA), capsid (CA), p2, nucleocapsid (NC) and p6 proteins of HIV-1 gag [8].

Biological context of EXOSC9

• We have previously demonstrated that PM-Scl-75, a component of the human exosome complex involved in RNA maturation and mRNA decay, can specifically interact with RNAs containing an AU-rich instability element [9].
• As such, it may be deduced that PMSCL1 sequences map to human chromosome 4q27 and the proximal portion of mouse chromosome (Chr) 3 where human and mouse cyclin A2 genes reside [10].
• In the case of C8166 cells, both a K197R and a E49K mutation were identified within the capsid (CA) protein and the p6 protein of Gag, respectively, while the other point mutation (A423G) was found within the putative DIS loop [11].
• The system required one of the p5 Rep proteins encoded by AAV (either Rep78 or Rep68) and a crude adenovirus (Ad)-infected HeLa cell cytoplasmic extract to catalyze origin of replication-dependent AAV DNA replication [12].
• Here we show that mutation of a single tyrosine residue, p5, in the carboxyl terminus of the erbB oncogene product allows it to become sarcomagenic in vivo and to transform fibroblasts in vitro [13].

Anatomical context of EXOSC9

• Approximately 30% of analogues at either Leu57 (p1), Ala60 (p4), or Asn62 (p6) residues exhibited TCR agonism to stimulate various magnitudes of proliferative responses in the T cell clone, and analogues exhibiting TCR antagonism are rare in these three residues [14].
• The data show that during chronic exposure of HeLa cells to AZT, a compensatory response was induced at the earlier passages (p5-p37), and by p71 there was widespread mitochondrial morphological damage, severe mtDNA depletion, and a substantial loss of mitochondrial membrane potential [15].
• METHODS: The trial was undertaken at a maternity teaching hospital in Adelaide, Australia, where 593 women less than 14 weeks' pregnant with symptoms of nausea or vomiting were randomized into 4 groups: traditional acupuncture, pericardium 6 (p6) acupuncture, sham acupuncture, or no acupuncture (control) [16].
• Another gag gene product, p6, plays an integral role in successful viral budding from the plasma membrane and inclusion of the accessory protein Vpr within newly budding virions [17].

Associations of EXOSC9 with chemical compounds

• RESULTS: IgE reactivities to new allergen components were not detected by CAP in treated patients after 15 weeks and a cumulative dose of approximately 65 microg of the major allergen Phl p 5 [18].
• Rep78 and Rep68 mutants deleted for the methionine at residue 225 showed decreased abilities to down-regulate both p5 and p19 transcript levels, while mutants containing a substitution of glycine for the methionine resembled the wild-type Rep78 [19].
• 9. Although there is evidence for a helix-forming tendency in the N-terminus of the protein, the experiments indicate that p6* has no overall stable secondary or tertiary structure with the single tryptophan exposed in aqueous solution [20].

Other interactions of EXOSC9

• While looking for proteins that bind to E12 and E47 by the yeast interaction trap, we isolated the rat (r) homologue of the human (h) polymyositis-scleroderma autoantigen (PM-Scl), which has been localized to the granular layer of the nucleolus and to distinct nucleocytoplasmic foci [7].

Analytical, diagnostic and therapeutic context of EXOSC9

• METHODS: Serum samples obtained from patients with the PM/scleroderma overlap syndrome and from patients with several other diseases were analyzed for the presence of autoantibodies reactive with recombinant PM-Scl-100 and PM-Scl-75 (both the original and the longer form) proteins, in an enzyme-linked immunosorbent assay (ELISA) [1].
• Der p 5-specific immunological responses including changes to specific immunoglobulin G and E (IgE) levels, the presence of cells in the bronchoalveolar lavage fluid (BALF), and AHR were assessed following this inhalational challenge [21].
• Women who received p6 acupuncture (p < 0.05) reported less nausea from the second week of the trial, and less dry retching (p < 0.001) from the third week compared with women in the no acupuncture control group [16].
• CEA was not detected after passage 5 (p5) but the concentration of CA19-9 did not decrease further after the first few serial passages in protein-free medium [22].
• Based on frequent co-sensitization patterns determined in 200 grass pollen-allergic patients, three recombinant hybrid molecules were developed by polymerase chain reaction-based mending of cDNAs coding for the major timothy grass pollen allergens (Phl p 1, Phl p 2, Phl p 5, Phl p 6) for vaccination against grass pollen allergy [23].

References