Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transcription factor Tax of the oncogenic human T-cell leukemia virus type 1 is likely to be responsible for viral replication in the host organism and for the induction of proliferation in infected cells. To investigate Tax-mediated transcription in vivo, we expressed Tax as well as CREB in Saccharomyces cerevisiae. The activity of these proteins was monitored by expression of a beta-galactosidase reporter gene, which was fused to two viral 21-bp repeats located upstream of the yeast cytochrome c1 oxidase minimal promoter. Coexpression of Tax and CREB in S. cerevisiae led to a 20-fold increase in beta-galactosidase activity in comparison with that in strains expressing either Tax or CREB alone. By screening a human cDNA library, we were able to demonstrate that the Tax transactivation assay using S. cerevisiae can be successfully applied to identify other cellular proteins forming ternary complexes with Tax and 21-bp repeats in vivo. Upon transformation in S. cerevisiae, 1 of 13,500 clones tested positive. Sequencing of the cDNA insert of the rescued plasmid revealed that this DNA encoded the ATF-1 protein. beta-Galactosidase induction was comparable to that of the Tax/CREB coexpression system. This indicates that Tax-mediated transcription is critically dependent on the presence of cellular CREB or ATF-1 in vivo. Stimulation of transcription initiation required an unmasked NH2 terminus of Tax. Fusion of Tax to the yeast Gal4 protein abolished the transactivation potential of Tax. Reconstitution of the transcriptional properties of viral Tax together with the cellular proteins of the ATF-1/CREB family in S. cerevisiae allows the functional characterization of these proteins in vivo.
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PMID:The oncoprotein Tax of the human T-cell leukemia virus type 1 activates transcription via interaction with cellular ATF-1/CREB factors in Saccharomyces cerevisiae. 889 66

The type II, class A macrophage scavenger receptor (SR-A) plays an important role in the pathogenesis of atherosclerosis and foam cell formation. However, its role in nonmacrophage cell lines remains unknown. To test the hypothesis that SR-A activity leads to proatherogenic changes in nonmacrophage cell lines, we generated Moloney murine leukemia virus- and vesicular stomatitis virus G protein-pseudotyped retroviruses containing SR-A type II cDNA, which were used for stable transfection of SR-A activity into mouse fibroblasts and rabbit aortic smooth muscle cells (SMCs). beta-Galactosidase-transfected cell lines were used as controls. Transfected cell lines expressed functional SR-A mRNA and protein. Expression of SR-A activity was stable for at least 9 months. By electron microscopy, transfected receptors were located in coated pits and in intracellular structures resembling endocytotic vesicles. Expression of SR-A on the cell surface was verified by flow cytometry and by uptake and degradation of (125)I-labeled acetylated low density lipoprotein (LDL). Increases of 5- to 25-fold and of 6- to 8-fold in the rate of acetylated LDL degradation were observed in transfected fibroblasts and SMCs, respectively, compared with beta-galactosidase-transfected control cell lines. Incubation of the transfected SMCs and fibroblasts with acetylated or oxidized LDL led to foam cell formation. Incubation with oxidized LDL also led to increased apoptosis and cell death. An altered morphology with increased cell size and granularity was observed in the most active SR-A SMC clones. It is concluded that stable overexpression of SR-A leads to foam cell formation and other proatherogenic changes in nonmacrophage cell lines. Stable SMC and fibroblast cell lines can be used as models for foam cell formation. The results also suggest that increased SR activity may play an important role in SMC-related pathology in atherosclerotic arteries.
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PMID:Retrovirus-mediated, stable scavenger-receptor gene transfer leads to functional endocytotic receptor expression, foam cell formation, and increased susceptibility to apoptosis in rabbit aortic smooth muscle cells. 1063