Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1.
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.
Kang
Dong-Chul
DC
Hallym University, Ilsong Institute of Life Science, 1605-4, Kwanyang-dong, Anyang, Kyeonggi-do, Republic of Korea.
Su
Zao-Zhong
ZZ
Sarkar
Devanand
D
Emdad
Luni
L
Volsky
David J
DJ
Fisher
Paul B
PB
D027322:Amino Acid Transport System X-AG / Q000235:genetics; D000906:Antibodies / Q000276:immunology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D027342:Excitatory Amino Acid Transporter 2; D005260:Female; D005333:Fetus; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics; D050491:Glutamate Plasma Membrane Transport Proteins; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D016366:Open Reading Frames / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D027981:Symporters / Q000235:genetics; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology
D027322:Amino Acid Transport System X-AG; D000906:Antibodies; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; D015699:HIV Envelope Protein gp120; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; C493397:SLC1A2 protein, human; D027981:Symporters; D014409:Tumor Necrosis Factor-alpha; D008156:Luciferases