4 results on '"Stancato C"'
Search Results
2. Regulation of CD4 expression via recycling by HRES-1/RAB4 controls susceptibility to HIV infection.
- Author
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Nagy G, Ward J, Mosser DD, Koncz A, Gergely P Jr, Stancato C, Qian Y, Fernandez D, Niland B, Grossman CE, Telarico T, Banki K, and Perl A
- Subjects
- Antigens, CD metabolism, Apoptosis, Base Sequence, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes virology, Chloramphenicol O-Acetyltransferase metabolism, Dependovirus genetics, Disease Susceptibility, Exons genetics, Flow Cytometry, Gene Products, tat pharmacology, Genes, Dominant, HIV Core Protein p24 metabolism, HIV Infections virology, HIV Long Terminal Repeat genetics, HeLa Cells, Humans, Introns genetics, Jurkat Cells, Lysosomes, Molecular Sequence Data, Mutagenesis, Site-Directed, Mutation genetics, Receptors, Transferrin metabolism, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Sequence Homology, Nucleic Acid, Transfection, rab4 GTP-Binding Proteins genetics, tat Gene Products, Human Immunodeficiency Virus, CD4 Antigens metabolism, Gene Expression Regulation, Viral, Gene Products, tat genetics, HIV Infections metabolism, HIV-1 pathogenicity, rab4 GTP-Binding Proteins metabolism
- Abstract
A novel 2986-base transcript encoded by the antisense strand of the HRES-1 human endogenous retrovirus was isolated from peripheral blood lymphocytes. This transcript codes for a 218-amino acid protein, termed HRES-1/Rab4, based on homology to the Rab4 family of small GTPases. Antibody 13407 raised against recombinant HRES-1/Rab4 detected a native protein of identical molecular weight in human T cells. HRES-1 nucleotides 2151-1606, located upstream of HRES-1/Rab4 exon 1, have promoter activity when oriented in the direction of HRES-1/Rab4 transcription. The human immunodeficiency virus, type 1 (HIV-1), tat gene stimulates transcriptional activity of the HRES-1/Rab4 promoter via trans-activation of the HRES-1 long terminal repeat. Transfection of HIV-1 tat into HeLa cells or infection of H9 and Jurkat cells by HIV-1 increased HRES-1/Rab4 protein levels. Overexpression of HRES-1/Rab4 in Jurkat cells abrogated HIV infection, gag p24 production, and apoptosis, whereas dominant-negative HRES-1/Rab4(S27N) had the opposite effects. HRES-1/Rab4 inhibited surface expression of CD4 and targeted it for lysosomal degradation. HRES-1/Rab4(S27N) enhanced surface expression, recycling, and total cellular CD4 content. Infection by HIV elicited a coordinate down-regulation of CD4 and up-regulation of HRES-1/Rab4 in PBL. Moreover, overexpression of HRES-1/Rab4 reduced CD4 expression on peripheral blood CD4+ T cells. Stimulation by HIV-1 of HRES-1/Rab4 expression and its regulation of CD4 recycling reveal novel coordinate interactions between an infectious retrovirus and the human genome.
- Published
- 2006
- Full Text
- View/download PDF
3. Increased prevalence of transfusion-transmitted virus and cross-reactivity with immunodominant epitopes of the HRES-1/p28 endogenous retroviral autoantigen in patients with systemic lupus erythematosus.
- Author
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Gergely P Jr, Pullmann R, Stancato C, Otvos L Jr, Koncz A, Blazsek A, Poor G, Brown KE, Phillips PE, and Perl A
- Subjects
- Adult, Amino Acid Sequence, Antibodies immunology, Antibody Affinity immunology, Antigens, Nuclear genetics, Autoantigens genetics, Circoviridae Infections epidemiology, Cross Reactions genetics, Cross Reactions immunology, Enzyme-Linked Immunosorbent Assay, Epitope Mapping, Epitopes, B-Lymphocyte genetics, Epitopes, B-Lymphocyte immunology, Female, Humans, Immunodominant Epitopes genetics, Lupus Erythematosus, Systemic blood, Lupus Erythematosus, Systemic virology, Male, Middle Aged, Molecular Sequence Data, Peptide Fragments chemical synthesis, Peptide Fragments chemistry, Peptide Fragments immunology, Prevalence, Retroviridae Proteins genetics, Sequence Homology, Amino Acid, Torque teno virus genetics, Viral Proteins genetics, Viral Proteins immunology, Viremia diagnosis, Viremia epidemiology, Antigens, Nuclear immunology, Autoantigens immunology, Circoviridae Infections immunology, Immunodominant Epitopes immunology, Lupus Erythematosus, Systemic immunology, Retroviridae Proteins immunology, Torque teno virus immunology
- Abstract
Objective: Systemic lupus erythematosus (SLE) patients produce autoantibodies to HRES-1/p28, a human endogenous retrovirus-encoded nuclear protein. To identify cross-reactive viral antigens capable of triggering autoreactivity, HRES-1/p28 epitopes were mapped by SLE antibodies., Methods: Forty-four peptides overlapping HRES-1/p28 and 13 viral peptides were synthesized on cellulose membrane and tested for recognition by antibodies from 16 HRES-1 Western blot seropositive SLE patients. Transfusion-transmitted virus (TTV) was detected by gene amplification in sera of 211 SLE patients, 78 healthy SLE family members, 199 unrelated healthy donors, and 91 rheumatoid arthritis (RA) patients., Results: HRES-1/p28 residues 41-55, 121-135, and 156-170 were recognized by 12/16 (75.0%), 11/16 (68.8%), and 9/16 lupus sera (56.25%) and considered immunodominant. HRES-1/p28 residues 121-135 harbor cross-reactive epitope with retroviral peptides and the 70 K U1snRNP lupus autoantigen. HRES-1/p28 residues 41-55 and 156-170 exhibited the highest prevalence of cross-reactivity with TTV peptide ORF2a (14/16, 87%). Prevalence of TTV DNA was increased in lupus patients (120/211) with respect to healthy (66/199; P < 0.0001) or RA controls (23/91; P < 0.0001). TTV prevalence in healthy lupus relatives (40/78) was decreased with respect to lupus patients (80/121; P = 0.0184) and increased with respect to unrelated healthy donors (66/199; P = 0.0026). HRES-1/p28 Western blot reactivity was observed in 12/23 TTV PCR-negative donors and 43/58 TTV PCR-positive donors (P < 0.0281)., Conclusions: Increased prevalence of TTV and molecular mimicry with HRES-1/p28 may contribute to generation of antinuclear antibodies and pathogenesis of SLE.
- Published
- 2005
- Full Text
- View/download PDF
4. Deletion of Ser-171 causes inactivation, proteasome-mediated degradation and complete deficiency of human transaldolase.
- Author
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Grossman CE, Niland B, Stancato C, Verhoeven NM, Van Der Knaap MS, Jakobs C, Brown LM, Vajda S, Banki K, and Perl A
- Subjects
- Cells, Cultured, Child, Enzyme Activation genetics, Enzyme Activation physiology, Enzyme Inhibitors pharmacology, Female, Fibroblasts chemistry, Fibroblasts enzymology, Fibroblasts metabolism, Gene Expression Regulation, Bacterial genetics, Gene Expression Regulation, Enzymologic drug effects, Gene Expression Regulation, Enzymologic genetics, Humans, Liver Cirrhosis enzymology, Liver Cirrhosis genetics, Lymphocytes chemistry, Lymphocytes enzymology, Lymphocytes metabolism, Models, Molecular, Mutagenesis, Site-Directed genetics, Proteasome Endopeptidase Complex physiology, Protein Conformation, RNA metabolism, Recombinant Proteins biosynthesis, Recombinant Proteins genetics, Sequence Deletion physiology, Serine physiology, Transaldolase biosynthesis, Transaldolase metabolism, Proteasome Endopeptidase Complex genetics, Sequence Deletion genetics, Serine genetics, Transaldolase deficiency, Transaldolase genetics
- Abstract
Homozygous deletion of three nucleotides coding for Ser-171 (S171) of TAL-H (human transaldolase) has been identified in a female patient with liver cirrhosis. Accumulation of sedoheptulose 7-phosphate raised the possibility of TAL (transaldolase) deficiency in this patient. In the present study, we show that the mutant TAL-H gene was effectively transcribed into mRNA, whereas no expression of the TALDeltaS171 protein or enzyme activity was detected in TALDeltaS171 fibroblasts or lymphoblasts. Unlike wild-type TAL-H-GST fusion protein (where GST stands for glutathione S-transferase), TALDeltaS171-GST was solubilized only in the presence of detergents, suggesting that deletion of Ser-171 caused conformational changes. Recombinant TALDeltaS171 had no enzymic activity. TALDeltaS171 was effectively translated in vitro using rabbit reticulocyte lysates, indicating that the absence of TAL-H protein in TALDeltaS171 fibroblasts and lymphoblasts may be attributed primarily to rapid degradation. Treatment with cell-permeable proteasome inhibitors led to the accumulation of TALDeltaS171 in whole cell lysates and cytosolic extracts of patient lymphoblasts, suggesting that deletion of Ser-171 led to rapid degradation by the proteasome. Although the TALDeltaS171 protein became readily detectable in proteasome inhibitor-treated cells, it displayed no appreciable enzymic activity. The results suggest that deletion of Ser-171 leads to inactivation and proteasome-mediated degradation of TAL-H. Since TAL-H is a regulator of apoptosis signal processing, complete deficiency of TAL-H may be relevant for the pathogenesis of liver cirrhosis.
- Published
- 2004
- Full Text
- View/download PDF
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