Abstract
We presently describe the full-length cloning and functional characterization of an HIV-1-inducible gene, astrocyte elevated gene (AEG)-1. Additionally, a novel method is outlined for producing tag-free recombinant protein in a baculovirus system and its use in producing AEG-1 protein. AEG-1 mRNA is expressed ubiquitously with higher expression in tissues containing muscular actin and its expression is increased in astrocytes infected with HIV-1 or treated with gp120 or tumor necrosis factor (TNF)-alpha. The mRNA encodes a single pass transmembrane protein of predicted molecular mass of 64-kDa and pI 9.3 that predominantly localizes in the endoplasmic reticulum and perinuclear region. Ectopic expression of AEG-1 inhibits excitatory amino acid transporter 2 (EAAT2) promoter activity with the potential to promote glutamate excitotoxicity and consequently HIV-1-associated dementia (HAD). AEG-1 expression is elevated in subsets of breast carcinomas, malignant gliomas and melanomas and it synergizes with oncogenic Ha-ras to enhance soft agar colony forming ability of non-tumorigenic immortalized melanocytes, documenting its tumor promoting activity. AEG-1 may affect tumor progression in multiple cell lineages by augmenting expression of the transformed phenotype and/or by inducing glutamate excitotoxicity in malignant glioma. In these contexts, an HIV-1-inducible gene, AEG-1, may contribute to multiple brain abnormalities, including HAD and tumor formation, by both common and distinct mechanisms.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Transport System X-AG / genetics
-
Antibodies / immunology
-
Astrocytes / drug effects
-
Astrocytes / metabolism*
-
Astrocytes / virology
-
Blotting, Northern
-
Blotting, Western
-
Brain
-
Cell Adhesion
-
Cell Adhesion Molecules
-
Cell Line
-
Cell Line, Tumor
-
Cell Proliferation
-
Cells, Cultured
-
Cloning, Molecular
-
DNA, Complementary / genetics
-
Excitatory Amino Acid Transporter 2
-
Female
-
Fetus
-
Gene Expression Profiling
-
Gene Expression Regulation*
-
Genetic Vectors / genetics
-
Glutamate Plasma Membrane Transport Proteins
-
HIV Envelope Protein gp120 / pharmacology
-
HIV-1 / growth & development*
-
Humans
-
Luciferases / genetics
-
Luciferases / metabolism
-
Male
-
Membrane Proteins
-
Microscopy, Fluorescence
-
Open Reading Frames / genetics
-
Promoter Regions, Genetic / genetics
-
RNA-Binding Proteins
-
Recombinant Proteins / immunology
-
Recombinant Proteins / metabolism
-
Symporters / genetics
-
Transfection
-
Tumor Necrosis Factor-alpha / genetics*
-
Tumor Necrosis Factor-alpha / metabolism
-
Tumor Necrosis Factor-alpha / pharmacology
-
Tumor Necrosis Factor-alpha / physiology
Substances
-
Amino Acid Transport System X-AG
-
Antibodies
-
Cell Adhesion Molecules
-
DNA, Complementary
-
Excitatory Amino Acid Transporter 2
-
Glutamate Plasma Membrane Transport Proteins
-
HIV Envelope Protein gp120
-
MTDH protein, human
-
Membrane Proteins
-
RNA-Binding Proteins
-
Recombinant Proteins
-
SLC1A2 protein, human
-
Symporters
-
Tumor Necrosis Factor-alpha
-
Luciferases