Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane cofactor protein (MCP; CD46), a widely distributed regulatory protein of the complement system, was analyzed for expression in polarized epithelial cells. Both a human and a simian (Vero C1008) cell line were found to contain endogenous MCP mainly on the basolateral surface. Transfected Madin-Darby canine kidney cells stably expressing human MCP delivered this protein also predominantly to the basolateral surface. A deletion mutant lacking the cytoplasmic tail was transported in a nonpolarized fashion, indicating that the targeting signal for the basolateral transport is located in the cytoplasmic domain. A characteristic feature of MCP is the presence of various isoforms that contain either of two different cytoplasmic tails as a consequence of alternative splicing. Two isoforms differing only in the cytoplasmic tail (tail 1 or 2) were analyzed for polarized expression in Madin-Darby canine kidney cells. Surface biotinylation, as well as confocal immunofluorescence microscopy, indicated that both proteins were transported to the basolateral surface. Because no sequence similarity has been observed, the two tails contain different basolateral targeting signals. A deletion mutant lacking the only tyrosine residue in tail 1 retained the polarized expression indicating that, in contrast to most basolateral sorting signals, the transport signal of the tail 1 isoform is not dependent on tyrosine. The maintenance of a targeting motif in two distinct cytoplasmic tails suggests that the basolateral expression of MCP in polarized epithelial cells is of physiological importance.
 ...
PMID:Two different cytoplasmic tails direct isoforms of the membrane cofactor protein (CD46) to the basolateral surface of Madin-Darby canine kidney cells. 870 45

Glomerular expression of intercellular adhesion molecule-1 (ICAM1) (CD54) and membrane cofactor protein (MCP; CD46) and positive infiltrating cells in leukocyte function associated antigen-1 (LFA1)alpha (CD11a) and C3bi receptors (CR3/CD11b, CR4/CD11c) were examined by the indirect immunoperoxidase method on 43 sets of repeated renal biopsy specimens from patients with immunoglobulin A nephropathy. Twenty-four-hour urine protein at the time of renal biopsy was also evaluated. Glomerular infiltration of LFA1alpha+ cells was significantly correlated with glomerular expression of ICAM1 (r = 0.494, P < 0.0001). Glomerular complement receptor type 4 (CR4)+ cells were significantly correlated with glomerular expression of MCP (r = 0.405, P < 0.0001). The glomerular expressions of ICAM1 and MCP were significantly correlated with each other (r = 0.700, P < 0.00001). The glomerular infiltrations of LFA1alpha+ and CR4+ cells were highly correlated with each other (r = 0.884, P < 0.00001), and both cell types were significantly correlated with urine protein (respectively, r = 0.426 and 0.478, P < 0.001 and 0.0001). When the change in these parameters between the time of the initial and follow-up biopsies was evaluated, there was a significant correlation between the change in glomerular expression of ICAM1 (DeltaICAM1) and MCP (DeltaMCP) as well as between the change in glomerular infiltration of LFA1alpha+ cells (DeltaLFA1alpha+) and CR4+ cells (DeltaCR4+). Both DeltaLFA1alpha+ and DeltaCR4+ were significantly correlated with the change in urine protein. These findings suggest that ICAM1/LFA1 interaction and MCP-mediated C3bi/C3biR interaction cooperate and participate in persistent glomerular infiltration of immune cells in immunoglobulin A nephropathy, and that these LFA1alpha+ and C3biR+ cells contribute to the induction of proteinuria.
 ...
PMID:Intercellular adhesion molecule-1/leukocyte function associated antigen-1-mediated and complement receptor type 4-mediated infiltration and activation of glomerular immune cells in immunoglobulin A nephropathy. 871 20

Membrane cofactor protein (MCP, CD46) of the complement system is a measles virus (MV) receptor. Human lymphocytes express a heavily glycosylated (H) and a lightly glycosylated (L) form of MCP, which confers a two-band profile on SDS-PAGE the ratio of which is controlled genetically and organ-specifically. In contrast, granulocytes express a single heavily glycosylated form regardless of lymphocyte MCP phenotype. We investigated susceptibility to MV of granulocytes and lymphocytes from individuals with different lymphocyte MCP phenotypes. In any individual, granulocytes were > 10-fold less susceptible to MV than lymphocytes, and the lymphocytes with predominant H form were generally less susceptible to those with an increasing amount of L form. Thus, lymphocytes always exhibit high susceptibility to MV compared to granulocytes in all individuals. This finding may explain the lymphopenia and immunosuppression observed secondary to MV infection.
 ...
PMID:Human lymphocytes are more susceptible to measles virus than granulocytes, which is attributable to the phenotypic differences of their membrane cofactor protein (CD46). 871 5

During measles virus (MV) infection, lymphopenia and immune suppression are observed in humans, yet the mechanisms underlying these effects remain unknown except that membrane cofactor protein (MCP, CD46) acts as a receptor for MV, accelerating entry of the virus into host cells. CD46 is a complement regulator, the role of which is to protect host cells from the autologous complement system. Thus, it encompasses complement-related and MV-mediated immune modulation. In this review, I discuss the structural and functional differences between CD46 on lymphocytes and on granulocytes, which partly explain the higher susceptibility of lymphocytes to MV than other blood cells to clarify the mechanisms of MV-mediated lymphopenia and immune suppression, and help resolve the T cell immunity dysfunction secondary to virus infection including HIV.
 ...
PMID:CD46, a complement regulatory protein/measles virus receptor, and its relation to hematological disorders. 885 67

CD46 (membrane cofactor protein, MCP) is a cell surface complement regulatory protein which may have an additional role in human sperm-egg interaction. A soluble form (sCD46) has also been detected in a number of biological fluids, most notably seminal plasma. The present study has employed a monoclonal antibody-based ELISA to assay sCD46 in reproductive tract fluids in normal and pathological conditions. Large amounts of sCD46 were detected in seminal plasma of both fertile and infertile men (combined mean, 4859 ng/ml). Vasectomized men had lower levels (mean, 2421 ng/ml), indicating contributory sources both before and after the vas deferens ligation site. Pre-colostrum also contained relatively high quantities (mean, 445 ng/ml), whereas breast milk (mean, 117 ng/ml), peritoneal fluid (mean, 154 ng/ml) and follicular fluid (mean, 107 ng/ml), as well as uterine (mean, 208 ng/ml), umbilical (mean, 166 ng/ml) and peripheral (mean, 206 ng/ml) blood plasma, had sCD46 levels within a comparable range. Amniotic fluid had low sCD46 concentrations (mean, 22 ng/ml). In endometriosis, peritoneal fluid levels of sCD46 were significantly raised (mean, 199 mg/ml). These results indicate distinctive fluid compartmentalisation of sCD46 consistent with a biological function in human reproductive tract fluids.
 ...
PMID:Soluble CD46 (membrane cofactor protein, MCP) in human reproductive tract fluids. 890 53

Rat oligodendrocytes spontaneously activate complement (C) and lack the C inhibitor CD59. As a consequence, rat oligodendrocytes are susceptible to lysis by autologous C in vitro. Expression of C inhibitors on human oligodendrocytes in vitro and other human glia has yet to be well characterized. We have previously shown expression at the mRNA level of the membrane inhibitors CD59, decay-accelerating factor (DAF; CD55) and membrane cofactor protein (MCP; CD46) in human astrocytes. We here examine the expression of membrane and secreted C inhibitors by the oligodendrocyte cell line, HOG. HOG cells abundantly expressed CD59, assessed at protein and mRNA level, and expressed DAF and MCP, albeit at a lower level. Expression of all three inhibitors was enhanced by incubation with interferon-gamma or with phorbol ester (PMA). Complement receptor type 1 (CR1; CD35) was neither expressed constitutively nor induced by cytokines. HOG also constitutively secreted C1-inhibitor, S-protein and clusterin. Factor H was secreted only after stimulation with cytokines. C4b binding protein was expressed at a very low level and was detected only at the mRNA level by reverse transcriptase-polymerase chain reaction (RT-PCR). For comparison, astrocyte expression of CD59, DAF, MCP and CR1 was confirmed at the mRNA and protein levels. HOG did not activate C spontaneously, as judged by the lack of deposition of C fragments, and were not lysed by C even after inhibition of CD59 and DAF using specific monoclonal antibodies.
 ...
PMID:Complement regulatory protein expression by a human oligodendrocyte cell line: cytokine regulation and comparison with astrocytes. 895 45

Complement in the respiratory tract protects the host from invading micoorganisms and other inhaled insults, but may damage normal tissue. Recently we reported that human respiratory epithelium from the nose to the alveoli expresses three cell-membrane regulators of complement activation: membrane cofactor protein (MCP, CD46), decay accelerating factor (DAF; CD55), and CD59. In this study we investigated whether two of these complement-regulatory proteins, DAF and CD59, protect human nasal epithelial cells from complement-mediated lysis. Treatment of nasal epithelial cells in suspension with 50% or 100% normal human serum (NHS) lysed small percentages of cells (8% and 16%, respectively). Addition of complement activators, rabbit serum antinasal epithelial cells (anti-NEC), or lipopolysaccharide (LPS) increased cell lysis in the presence of 50% NHS in a dose-dependent manner up to 50% and 35% lysis, respectively. Human serum deficient in C3 or C7 did not lyse nasal epithelial cells even in the presence of anti-NEC. To assay the contribution of DAF and CD59 to cell protection against lysis, nasal epithelial cells in suspension were treated with appropriate blocking antibodies. Both anti-DAF and anti-CD59 markedly increased the susceptibility of human nasal epithelial cells to lysis by complement. At 50% NHS, anti-DAF and anti-CD59 antibodies increased epithelial cell lysis from 8% to 24% and 67%, respectively. A similar pattern of response to complement was demonstrated by monolayers of substrate-anchored cultured cells. These results indicate that DAF and CD59 protect human nasal epithelial cells from complement-mediated lysis; however, intense activation of complement may overcome this protection, leading to cell death and tissue injury. We speculate that imbalance between complement regulation and complement activation in the human respiratory tract in disease may result in tissue injury and impaired tissue function.
 ...
PMID:Protection of human nasal respiratory epithelium from complement-mediated lysis by cell-membrane regulators of complement activation. 896 67

Ovarian cancer has features that makes it well-suited for MAb adjuvant immunotherapy. Several of the MAbs used in clinical trials mediate cancer cell destruction by activation of complement (C). In this study, therefore, we examined the ability of ovarian-tumor cells to resist C attack. We found that the C regulators membrane cofactor protein (MCP, CD46) and protectin (CD59) were strongly expressed in the tumor cells in all 28 benign and malignant tumors examined. Decay-accelerating factor (DAF; CD55) was more heterogeneously expressed, and only 75% of the tumors exhibited a moderate amount of DAF in the tumor cells. In adenoma cells, CD59 and DAF were preferentially located apically, while in adenocarcinoma cells they were expressed also at the basolateral cell surface. The ovarian-carcinoma cell lines SK-OV-3, Caov-3, SW626 and PA-1 expressed both the 58- and the 68-kDa isoforms of MCP. DAF was present as a glycosyl-phosphatidylinositol(GPI)-anchored 70-kDa glycoprotein. The surface-expression level of DAF varied, and correlated with the vulnerability of the cells to C-mediated lysis. CD59 was expressed as a GPI-linked 19- to 25-kDa protein exhibiting multiple glycosylation variants. The surface expression of CD59 correlated with the amount of the main 1.9 + 2.1-kb CD59 mRNA transcripts. Neutralization of CD59 with an anti-CD59 MAb significantly enhanced C-mediated killing of the cell lines. Low expression of C regulators on the PA-1 teratocarcinoma cell line was associated with high sensitivity to C lysis. Thus, the expression of C regulators on malignant ovarian cells may constitute a tumor escape mechanism, and is a critical parameter to be examined when MAb therapy is being considered.
 ...
PMID:Complement-regulatory proteins in ovarian malignancies. 898 85

We isolated a 1257-bp cDNA encoding a membrane cofactor protein (MCP, CD46)/measles virus (MV) receptor-like protein from a cDNA library of Vero cells, in which wild MV strains were established. Vero cells contain MCP mRNA splice products encoding different cytoplasmic tails like human cells. The deduced amino acid sequence of the cDNA was 86% identical to that of human MCP. Vero cell MCP expressed on CHO cells was recognized by monoclonal antibodies against human MCP, and served as a potent MV receptor. In addition, Vero MCP was as effective as human MCP in human factor I-mediated C3b cleavage. Thus, the high MV susceptibility of Vero cells can in part be attributed to an MCP-like molecule that is structurally and functionally similar to human MCP.
 ...
PMID:Molecular cloning of a complementary DNA for a membrane cofactor protein (MCP, CD46)/measles virus receptor on Vero cells and its functional characterization. 899 35

A panel of mAbs were raised against pig lymphocytes. Seven mAbs immunoprecipitated a 50- to 60-kDa membrane-bound protein. This protein, termed JM4C8-Ag, was expressed on a wide variety of cells, including all circulating cells and cells of fibroblast, epithelial, and endothelial origin. The JM4C8-Ag was transmembrane-anchored and glycosylated. One of the Abs was used in immunoaffinity chromatography to isolate JM4C8-Ag from erythrocyte membranes. N-terminal amino acid analysis through the first 28 residues showed a 43% homology with the human complement regulatory molecule membrane cofactor protein (MCP; CD46). The purified protein had cofactor activity for factor I-mediated cleavage of human and pig C3b, confirming its identity as the pig analogue of human MCP. The purified protein also strongly inhibited lysis of rabbit erythrocytes by human and pig complement after activation of the classical or alternative pathway. This is the first report of a nonprimate analogue of MCP. The presence of a resident MCP on pig cells capable of acting as a cofactor in the control of human complement activation has consequences for the use of pig organs in xenotransplantation.
 ...
PMID:Purification and characterization of the pig analogue of human membrane cofactor protein (CD46/MCP). 902 6


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>