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The C terminus of HIV-1 Tat modulates the extent of CD178-mediated apoptosis of T cells.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2005 Nov 18; Vol. 280 (46), pp. 38376-82. Date of Electronic Publication: 2005 Sep 09. - Publication Year :
- 2005
-
Abstract
- HIV infection and the progression to AIDS are characterized by the depletion of CD4(+) T cells through apoptosis of the uninfected bystander cells and the direct killing of HIV-infected cells. This is mediated in part by the human immunodeficiency virus, type 1 Tat protein, which is secreted by virally infected cells and taken up by uninfected cells and CD178 gene expression, which is critically involved in T cell apoptosis. The differing ability of HIV strains to induce death of infected and uninfected cells may play a role in the clinical and biological differences displayed by HIV strains. We chemically synthesized the 86-residue truncated short variant of Tat and its full-length form. We show that the trans-activation ability of Tat at the long terminal repeat does not correlate with T cell apoptosis but that the ability of Tat to up-regulate CD178 mRNA expression and induce apoptosis in T cells is critically dependent on the C terminus of Tat. Moreover, the greater 86-residue Tat-induced apoptosis is via the extrinsic pathway of CD95-CD178.
- Subjects :
- CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes virology
Cell Separation
Fas Ligand Protein
Flow Cytometry
HeLa Cells
Humans
Jurkat Cells
Leukocytes, Mononuclear cytology
Leukocytes, Mononuclear virology
Mutation
Protein Structure, Tertiary
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Transcriptional Activation
Up-Regulation
fas Receptor biosynthesis
Apoptosis
Gene Expression Regulation
Gene Products, tat chemistry
Gene Products, tat physiology
Membrane Glycoproteins physiology
T-Lymphocytes metabolism
Tumor Necrosis Factors physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 280
- Issue :
- 46
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 16155003
- Full Text :
- https://doi.org/10.1074/jbc.M506630200