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Biomedical subjects

A Elkeles

Publications and source records attributed to A Elkeles.

At least 19 recordsLinked to original sources
PubMed1999

The c-fos proto-oncogene is a target for transactivation by the p53 tumor suppressor.

The p53 tumor suppressor gene is mutated in over 50% of human cancers, resulting in inactivation of the wild-type (wt) p53 protein. The most notable biochemical feature of p53 is its ability to act as a sequence-specific transcriptional activator. Through use of the suppression subtractive hybridization differential screening technique, we identified c-fos as a target for transcriptional stimulation by p53 in cells undergoing p53-mediated apoptosis. Overexpression of wt p53 induces c-fos mRNA and protein. Moreover, in vivo induction of c-fos in the thymus following whole-body exposure to ionizing radiation is p53 dependent. p53 responsiveness does not reside in the basal c-fos promoter. Rather, a distinct region within the c-fos gene first intron binds specifically to p53 and confers upon the c-fos promoter the ability to become transcriptionally activated by wt p53. Identification of c-fos as a specific target for transcriptional activation by p53 establishes a direct link between these two pivotal regulatory proteins and raises the possibility that c-fos contributes to some of the biological effects of p53.

Amino Acid Sequence↗
PubMed1998

The Mdm2 oncoprotein interacts with the cell fate regulator Numb.

The Mdm2 oncoprotein is a well-known inhibitor of the p53 tumor suppressor, but it may also possess p53-independent activities. In search of such p53-independent activities, the yeast two-hybrid screen was employed to identify Mdm2-binding proteins. We report that in vitro and in transfected cells, Mdm2 can associate with Numb, a protein involved in the determination of cell fate. This association causes translocation of overexpressed Numb into the nucleus and leads to a reduction in overall cellular Numb levels. Through its interaction with Numb, Mdm2 may influence processes such as differentiation and survival. This could potentially contribute to the altered properties of tumor cells which overexpress Mdm2.

Amino Acid Sequence↗
PubMed1997

A novel p53-inducible gene, PAG608, encodes a nuclear zinc finger protein whose overexpression promotes apoptosis.

The biological effects of the p53 tumor suppressor protein are elicited, at least in part, through sequence-specific transactivation of a battery of target genes. The differential display method was employed towards identifying additional p53 target genes, with emphasis on genes whose induction may contribute to p53-mediated apoptosis. We report here the cloning of a novel p53-inducible gene, designated PAG608. PAG608 transcripts are induced by DNA damage in a p53-dependent manner. PAG608 encodes a nuclear zinc finger protein, which appears to localize preferentially to nucleoli when expressed at moderate levels in transfected cells. Transient overexpression of PAG608 in human tumor-derived cells leads to distinctive changes in nuclear morphology, and can promote apoptosis. Together with additional p53 target genes, PAG608 may therefore play a role in mediating the biological activities of p53.

Amino Acid Sequence↗
PubMed1997

Functional differences among wheat voltage-dependent anion channel (VDAC) isoforms expressed in yeast. Indication for the presence of a novel VDAC-modulating protein?

VDAC is a voltage-gated anion channel located in the mitochondrial outer membrane, presumably participating in controlling aerobic metabolism. Three distinct wheat vdac cDNAs were expressed in a vdac-minus yeast strain and successfully complemented its defective phenotype. The growth curves of these transformants were different. The wheat channel isoforms were functionally characterized following purification from yeast mitochondria and reconstitution into soybean phospholipid planar membranes. All three isoforms yielded voltage-dependent anion channels with electrophysiological parameters comparable to known VDACs. Isoform-related functional features (specific conductance levels, kinetics, and gating behaviors) are reported for the first time in VDACs. The presence (or absence) of protease inhibitors during the purification procedure, and the use of Pronase on reconstituted channels, strongly suggest that some of the unique wheat VDAC properties are due to co-purification of a yeast channel-modulating protein. Its effects, different from the reported functional interactions of the channel with hexo- or creatine kinases, could not be mimicked by the protein termed VDAC modulator, indicating the presence of a novel VDAC modulator. In addition to strengthening VDAC presumed role in metabolism, the functional diversity of the channels (as shown here in two different systems) implies a highly dynamic outer membrane permeability. Our results are consistent with VDAC functioning as a heteromer including one pore protein and other modulating subunits.

Animals↗
PubMed1995

Multiple cDNAs of wheat voltage-dependent anion channels (VDAC): isolation, differential expression, mapping and evolution.

The mitochondrial outer membrane of eukaryotic cells contains voltage-dependent anion channels (VDAC) also termed porins. Three cDNAs from wheat (Triticum aestivum) were isolated and sequenced (Tavdac 1-3). They share 65% similarity of their amino acid sequences, and therefore they probably represent isoforms. The deduced amino acid sequence of one of the cDNAs was found to be identical to the purified VDAC protein from wheat mitochondria [8]. Secondary structure analysis of the deduced amino acid sequences of the three vdac cDNAs revealed a characteristic alpha helix at their N-terminal and beta-barrel cylinders characteristic of VDAC channels. The Tavdac cDNAs are differentially expressed in meristematic tissues. The transcript levels of Tavdac 1 in all wheat tissues is at least 2.5-fold higher than Tavdac 2 and Tavdac 3. Tavdac 2 has a low level of expression in all floral tissues whereas Tavdac 3 is highly expressed in anthers. This is the first report on differential expression of vdac genes in plants. The Tavdac genes have been mapped on the wheat genome. Tavdac 1 is located on the long arm of chromosome 5, Tavdac 2 on the long arm of chromosome 1 and Tavdac 3 on the long arm of chromosome 3. A phylogenetic reconstruction indicates that vdac genes underwent numerous duplication events throughout their evolution. All duplications occurred after the separation of plants from animals and fungi, and no orthologous genes are shared among phyla. Within plants, some of the vdac gene duplications probably occurred before the monocotydelon-dicotydelon split.

Amino Acid Sequence↗
PubMed1994

Azide-resistant mutants in Acinetobacter calcoaceticus A2 are defective in protein secretion.

Azide, an inhibitor of ATPase, and a specific inhibitor of protein export was used in order to select for protein secretion mutants in Acinetobacter calcoaceticus A2. Two such mutants were isolated that were azide-resistant and defective in the general protein transport system. The mutation also conferred additional phenotypic changes, including an inability to grow on minimal media or at 40 degrees C. The existence of protein secretion mutants with a selectable phenotype may be useful for the genetic study of protein export.

Acinetobacter calcoaceticus↗
PubMed1994

Production and Secretion of the Polysaccharide Biodispersan of Acinetobacter calcoaceticus A2 in Protein Secretion Mutants.

Biodispersan is an extracellular anionic polysaccharide produced by Acinetobacter calcoaceticus A2 that changes the surface properties of limestone and acts both as a dispersant and as a grinding aid (E. Rosenberg, C. Rubinovitz, A. Gottlieb, S. Rosenhak, and E. Z. Ron, Appl. Environ. Microbiol. 54:317-322, 1988; E. Rosenberg, C. Rubinovitz, R. Legmann, and E. Z. Ron, Appl. Environ. Microbiol. 54:323-326, 1988; E. Rosenberg, Z. Schwartz, A. Tenenbaum, C. Rubinovitz, R. Legmann, and E. Z. Ron, J. Dispersion Sci. Technol. 10:241-250, 1989). Extracellular fluid also contains a high concentration of secreted proteins that create problems in the purification and application of biodispersan. In order to obtain preparations of biodispersan that contained smaller amounts of protein, we selected mutants of strain A2 that were defective in protein secretion. These mutants produced equal, or even higher, levels of total biodispersan compared with those of the parental strain. Moreover, although there was a significant drop in the concentration of extracellular proteins in the medium, the secretion of biodispersan was unaffected. These results suggest that secretion mutants are potentially useful for the production of extracellular polysaccharides.

Journal Article↗
PubMed1977

Metabolic behavior of alpha-ray activity in large human arteries: relationship to atherosclerosis.

The paradoxic biologic behavior of tissue calcium metabolism is emphasized. Although calcium salts are essential for the development of bones, they also contribute to aging of the large human arteries. The heavy elements providing alpha-ray activity tend to be metabolized like calcium. The concept of an osteoporosis-atherosclerosis relationship led to a series of investigations in which ash content and alpha-ray activity were examined in abdominal aortas, coronary arteries, pulmonary arteries and, for comparison, in bones and ventral costal cartilages. Both ash content and alpha-ray activity rise with age in the aorta and in the coronary arteries, but there is no such increase in the pulmonary arteries. A statistically significant correlation between ash content and alpha-ray activity has been found only in aortas and coronary arteries. This correlation is even closer in the coronary arteries of subjects who die of coronary artery disease and in the aortas of the elderly. Wet tissue alpha-ray activity in an aorta with severe atherosclerosis may be 220 times higher than in an aorta without significant atherosclerosis. Alpha-activity in bones and in ventral costal cartilages tends to decline in advancing years, though in the cartilages the calcium deposits increase with age. Our studies reveal a close relationship between atherogenesis and the unique metabolic behavior of alpha-ray radiation in the large human arteries.

Age Factors↗
PubMed1976

Observations on the natural history of atherogenesis.

Longstanding scoliosis of the lumbar spine with convexity to the left leads to severe atherosclerosis in the adjacent segment of the abdominal aorta. By contrast, the lateral wall of the ascending aorta, which is free to pulsate, usually is not affected even in very old persons. This relative immunity, however, is not maintained in cases of syphilitic mesaortitis; damage to the elastic tissues of the media leads to atherosclerosis. Man is the only mammal known to be highly susceptible to severe atherosclerosis. The concept is advanced that the erect posture of man, which leads to the physiologic anterior curvature of the lumbar spine, predisposes to atheroma formation in the abdominal aorta, particularly in women. Evidence for the osteoporosis-atherosclerosis concept is presented. Sustained muscular activity starting early in life can delay osteoporosis and atherosclerosis. A possible mechanism for the onset and gradual progression of physiologic osteoporosis is suggested. The concept of atherogenesis advanced here is based on observations which suggest a correlation of aging processes in the mesenchymal tissues. These aging processes, in conjunction with mechanical factors partly caused by the erect posture, may account for the unique susceptibility of man to severe atherosclerosis.

Aged↗