Disease relevance of Mup1

• Role of hemagglutinin cleavage and expression of M1 protein in replication of A/WS/33, A/PR/8/34, and WSN influenza viruses in mouse brain [1].
• The findings suggest that availability of M1 protein is a factor influencing the extent or rate of assembly of potentially infectious (i.e., trypsin-activated) progeny virions in mouse brains and that in this respect the two non-neurovirulent strains differ from WSN quantitatively rather than qualitatively [1].
• Genomic analysis of matrix gene and antigenic studies of its gene product (M1) of a swine influenza virus (H1N1) causing chronic respiratory disease in pigs [2].
• It was unexpectedly found that 5'-termini of the M1 and M2 genes ended with 5'-ACUUUU and 5'-UCUUUU, respectively, instead of 5'-GCUUUU, which is present on most mRNAs of other avian reoviruses (ARV) [3].
• Enantiomers of oxybutynin: in vitro pharmacological characterization at M1, M2 and M3 muscarinic receptors and in vivo effects on urinary bladder contraction, mydriasis and salivary secretion in guinea pigs [4] .

High impact information on Mup1

• Transcription of cloned genes for alpha 2u globulin, growth hormone, mouse mammary tumour virus and lysozyme can be induced in vivo by steroid hormones after transfer to cells containing steroid hormone receptors [5].
• Three to ten copies of the alpha 2u globulin genes were detected several tk+ clones, over 50% of which could be induced with dexamethasone, the produce alha 2u globulin mRNA and protein [6].
• Four potential modes of action for Perc-induced renal tumorigenesis are: 1) peroxisome proliferation, 2) alpha-2u-globulin nephropathy, 3) genotoxicity leading to somatic mutation, and 4) acute cytotoxicity and necrosis leading to cell proliferation [7].
• By the use of an M6 monoclonal antibody, which crossreacts with 20 different M protein types, and antibodies to the N-acetyl glucosamine determinant of the cell wall, we have been able to identify the M protein molecules released from the streptococcal cell wall with muralytic enzymes, particularly group C phage-associated lysin [8].
• It can therefore be concluded that the IFN-alpha gene cluster is situated on chromosome 4 near the H-15 locus, between loci Mup-1 and b [9].

Chemical compound and disease context of Mup1

• The human oral commensal Streptococcus gordonii was engineered to surface express a 204-amino acid allergen from hornet venom (Ag5.2) as a fusion with the anchor region of the M6 protein of Streptococcus pyogenes [10].
• Surprisingly, both LLnL and lactacystin increased rather than inhibited the expression of a cytosolically transcribed and TAP-dependent peptide from the influenza A virus M1 protein [11].
• A considerable body of scientific data has indicated that the renal toxicity of d-limonene results from the accumulation of a protein, alpha 2u-globulin, in male rat kidney proximal tuble lysosomes [12].

Biological context of Mup1

• The tropomodulin (Tmod) gene maps to chromosome 4, closely linked to Mup1 [13].
• Real-time polymerase chain reaction analysis confirmed these findings and showed, for the high-fat diet groups, an identical expression pattern for Mup1, whereas Mod1 showed an opposed gene expression pattern for the high-fat diet groups [14].
• The expression of a defective LPS response gene Lps and the major urinary protein (Mup-1) are concordantly inherited in backcross (C3H/HeJ x C57BL/6J)F1 x C3H/HeJ mice, indicating genetic linkage of these loci [15].
• However, a Southern blot analysis of the corresponding genomic DNA sequences showed that the M2 gene was amplified fivefold but the M1 gene was still single copy [16].
• Mammalian ribonucleotide reductase consists of two nonidentical subunits, proteins M1 and M2, which are differentially regulated during the cell cycle [16].

Anatomical context of Mup1

• Unchanged Am-80 was present in high amounts in the plasma and bile or feces of all animal species tested except in rat bile, in which Am-80 was predominantly detected in the form of its taurine conjugate (M-6) [17].
• Early increases in M1 and/or M2 message and protein levels were observed only in malignant cell lines [18].
• Using potent Na+/H+ exchange inhibitors we show for normal mouse bone marrow-derived macrophages that this activity is required for the colony-stimulating factor-1-induced gene expression of the M1 and M2 subunits of ribonucleotide reductase, an enzyme critical for DNA synthesis [19].
• Immunostaining revealed low levels of M1 and NS1 expression only in astrocytes, not in oligodendrocytes and neurons [20].
• IFN-beta induction in reovirus-infected cardiac myocyte cultures correlated with viral myocarditic potential (P = 0.006) and was associated with the reovirus M1, S2, and L2 genes [21].

Associations of Mup1 with chemical compounds

• The relative levels of synthesis of these proteins with respect to each other in the presence of testosterone is regulated by the Mup-a locus located on chromosome 4 [22].
• The hydroxyurea-resistant TA3 cells contained a 50- to 100-fold excess of the M2 mRNAs over that of the parent cells and a 10-fold excess of the M1 mRNA [16].
• Metabolite 2 (M2) was also a glucuronide (Mr 456) but appeared to be an unusual isomer of M1 [23].
• Mice cleared flavone acetic acid much more slowly than patients (289 ml/h/m2 after 600 mg/m2 i.p. versus 2.3 liters/h/m2 after 4.8 g/m2-1-h i.v. infusion) without producing M1 or M2 [23].
• Transcription runoff assays suggest a diminution of transcription rate for the M2 gene in S49 cells treated with dibutyryl cyclic AMP and a transient decline in the M1 transcription rate [24].
• Recombinant MUP1 directly decreased glucose production in primary hepatocyte cultures by inhibiting the expression of gluconeogenic genes [25].

Physical interactions of Mup1

• Binding of androgen-receptor complexes to alpha 2u-globulin genes and to the long terminal repeat of mouse mammary tumor virus [26].
• Linkage studies showed that both of the major NZB and NZW genes are loosely linked to the H-2 complex but not to either the Mup-1 or coat color gene loci examined [27].

Other interactions of Mup1

• Linkage was tested for four different genes on mouse chromosome 4: Aco-1, Mup-1, b, and Ifb [28].
• Taurine conjugation reaction of unchanged Am-80 and hydroxy-Am-80 (to form M-6 and both M-1 and M-2, respectively) was distinct in rats and dogs, but, hardly detected in mice and rabbits [17].
• Progeny studies suggested that a single dominant locus (Imh-1) of NZB strain, which is loosely linked to brown-black coat colour locus b and Mup-1 locus on chromosome 4, determines the IgM class hypergammaglobulinaemia [29].
• This variation does not correlate with variation at Mup-a, a locus that controls the ratio of the three MUPs in urine from androgen-induced mice [30].
• Both M1 and M2 genes were also induced, with increased mRNA levels appearing 2 h after zinc treatment, or 1 h after TGF-beta 1 message levels were clearly elevated [18].

Analytical, diagnostic and therapeutic context of Mup1

• Cells in immunostained sections and appropriate bands in Western blots (immunoblots) of viral proteins electrophoretically separated from lysates of PR8-infected brains reacted with antibody to nucleoprotein but not to M1 protein [1].
• This report documents the first sequence analysis of the entire M1, M2, and M3 genome segments of the muscovy duck reovirus (DRV) S14 [3].
• Northern blot analysis showed a decreased production of viral mRNA in endothelial cells infected with type 3 Dearing reovirus, but not type 1 Lang. Thus, we have identified a viral gene (the M1 gene) responsible for determining the difference in growth capacity of the two reovirus isolates in cultured endothelial cells [31].
• In a competitive radioimmunoassay using [3H]aflatoxin B1, 3 pmol (1 ng) of aflatoxin B1, aflatoxin B2, or aflatoxin M1 caused 50% inhibition with this antibody [32].
• The expression of the alpha 2u globulin transgene in the liver was abolished by castration and fully restored after testosterone replacement [33].

References