The 3′-UT of the ubiquitous mRNA of human CD46 confers selective suppression of protein production in murine cells

Shida, Kyoko; Nomura, Midori; Matsumoto, Misako; Suzuki, Yasuhiko; Toyoshima, Kumao; Seya, Tsukasa

doi:10.1002/(sici)1521-4141(199911)29:11<3603::aid-immu3603>3.0.co;2-r

Cited by 12 publications

(9 citation statements)

References 15 publications

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“…In humans, various splice isoforms of CD46 are known to exist within an organ and also in an organ-specific manner (35). In mice, a 1.5-kb message is expressed predominantly in testis, as determined by Northern blot analysis (42).…”

Section: Resultsmentioning

confidence: 99%

Disruption of Mouse CD46 Causes an Accelerated Spontaneous Acrosome Reaction in Sperm

Inoue

Ikawa

Nakanishi

et al. 2003

Molecular and Cellular Biology

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127

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Human membrane cofactor protein (MCP, CD46) is a ubiquitously expressed protein known to protect cells from complement attack. Interestingly, when we examined the expression of mouse CD46, which we recently cloned, the message was found only in testis and the protein was found on the inner acrosomal membrane of sperm. In order to elucidate the function of CD46, we produced mice carrying a null mutation in the CD46 gene by using homologous recombination. Despite the absence of CD46, the mice were healthy and both sexes were fertile. However, to our surprise, the fertilizing ability of males appeared to be facilitated by disruption of the CD46 gene, as the average number of pups born from CD46 ؊/؊ males was significantly greater than that of wild-type males. It was also revealed that the incidence of the spontaneous acrosome reaction doubled in CD46 ؊/؊ sperm compared to that in wild-type sperm. It was assumed that this increase caused the heightened fertilizing ability found in CD46 ؊/؊ sperm. These data suggest that CD46 may have some role in regulating sperm acrosome reaction.

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Section: Resultsmentioning

confidence: 99%

Disruption of Mouse CD46 Causes an Accelerated Spontaneous Acrosome Reaction in Sperm

Inoue

Ikawa

Nakanishi

et al. 2003

Molecular and Cellular Biology

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127

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“…Total RNA was isolated from either MV-infected or noninfected cells according to a standard protocol using guanidium-HCl and acid-phenol/chloroform (39). cDNA was synthesized with SuperScript II RNase H-Reverse Transcriptase (Life Technologies).…”

Section: Rt-pcr and Quantitative Rt-pcrmentioning

confidence: 99%

“…As a control for the presence of amplifiable RNA, GAPDH primers were used to amplify a 249-bp segment as previously described (34). Amplified PCR products were analyzed by agarose gel (2.0%) containing ethidium bromide (39).…”

Section: Rt-pcr and Quantitative Rt-pcrmentioning

confidence: 99%

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Functional Modulation of Human Macrophages Through CD46 (Measles Virus Receptor): Production of IL-12 p40 and Nitric Oxide in Association with Recruitment of Protein-Tyrosine Phosphatase SHP-1 to CD46

Kurita-Taniguchi

Fukui

Hazeki

et al. 2000

The Journal of Immunology

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Human CD46, formerly membrane cofactor protein, binds and inactivates complement C3b and serves as a receptor for measles virus (MV), thereby protecting cells from homologous complement and sustaining systemic measles infection. Suppression of cell-mediated immunity, including down-regulation of IL-12 production, has been reported on macrophages (Mφ) by cross-linking their CD46. The intracellular events responsible for these immune responses, however, remain unknown. In this study, we found that 6- to 8-day GM-CSF-treated peripheral blood monocytes acquired the capacity to recruit protein-tyrosine phosphatase SHP-1 to their CD46 and concomitantly were able to produce IL-12 p40 and NO. These responses were induced by stimulation with mAbs F(ab′)2 against CD46 that block MV binding or by a wild-type MV strain Kohno MV strain (KO; UV treated or untreated) that was reported to induce early phase CD46 down-regulation. Direct ligation of CD46 by these reagents, but not intracellular MV replication, was required for these cellular responses. Interestingly, the KO strain failed to replicate in the 6- to 8-day GM-CSF-cultured Mφ, while other MV strains replicated to form syncytia under the same conditions. When stimulated with the KO strain, rapid and transient dissociation of SHP-1 from CD46 was observed. These and previous results provide strong evidence that CD46 serves as a signal modulatory molecule and that the properties of ligands determine suppression or activation of an innate immune system at a specific maturation stage of human Mφ.

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“…We next focused on the 3h-flanking region of murine CD46 due to the fact that in our previous study we detected an inhibitory effect in the 3h-untranslated region of human CD46 gene in mouse cell lines, but not in primate cells [36]. The 2.0 kb 3h-flanking sequence is shown in Figure 3.…”

Section: Silencer Assay Of the Human And Murine Cd46 Genementioning

confidence: 99%

Identification and characterization of a silencer regulatory element in the 3′-flanking region of the murine CD46 gene

Nomura

Tsujimura

Begum

et al. 2000

Biochemical Journal

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The murine membrane cofactor protein (CD46) gene is expressed exclusively in testis, in contrast to human CD46, which is expressed ubiquitously. To elucidate the mechanism of differential CD46 gene expression among species, we cloned entire murine CD46 genomic DNA and possible regulatory regions were placed in the flanking region of the luciferase reporter gene. The reporter gene assay revealed a silencing activity not in the promoter, but in the 3´-flanking region of the gene and the silencer-like element was identified within a 0.2-kb region between 0.6 and 0.8kb downstream of the stop codon. This silencer-like element was highly similar to that of the pig MHC class-I gene. The introduction of a mutation into this putative silencer element of murine CD46 resulted in an abrogation of the silencing effect. Electrophoretic mobility-shift assay indicated the presence of the binding molecule(s) for this silencer sequence in murine cell lines and tissues. A size difference of the protein–silencer-element complex was observed depending upon the solubilizers used for preparation of the nuclear extracts. A mutated silencer sequence failed to interact with the binding molecules. The level of the binding factor was lower in the testicular germ cells compared with other organs. Thus the silencer element and its binding factor may play a role in transcriptional regulation of murine CD46 gene expression. These results imply that the effects of the CD46 silencer element encompass the innate immune and reproductive systems, and in mice may determine the testicular germ-cell-dominant expression of CD46.

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The 3′-UT of the ubiquitous mRNA of human CD46 confers selective suppression of protein production in murine cells

Cited by 12 publications

References 15 publications

Disruption of Mouse CD46 Causes an Accelerated Spontaneous Acrosome Reaction in Sperm

Disruption of Mouse CD46 Causes an Accelerated Spontaneous Acrosome Reaction in Sperm

Functional Modulation of Human Macrophages Through CD46 (Measles Virus Receptor): Production of IL-12 p40 and Nitric Oxide in Association with Recruitment of Protein-Tyrosine Phosphatase SHP-1 to CD46

Identification and characterization of a silencer regulatory element in the 3′-flanking region of the murine CD46 gene

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