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Biomedical subjects

D Ginsberg

Publications and source records attributed to D Ginsberg.

At least 37 records · Page 2Linked to original sources
PubMed1994

E2F-4, a new member of the E2F transcription factor family, interacts with p107.

The E2F family of transcription factors has been implicated in the regulation of cell proliferation, and E2F-binding sites are present in the promoters of several growth-regulating genes. E2F family members are functionally regulated, in part, by complex formation with one or more members of the nuclear pocket protein family, RB, p107, and p130. Pocket protein regulation of E2F likely contributes to normal cellular growth control. While the three cloned species of E2F, E2F-1, E2F-2, and E2F-3, are known to be targets of RB interaction, no E2F species has yet been shown to be a specific p107 or p130 target. Here, we describe the cloning of a new member of the E2F family, E2F-4, which forms heterodimers with a member(s) of the DP family and, unlike some family members, is present throughout the cell cycle and appears to be a differentially phosphorylated p107-binding partner. p107 binding not only can be linked to the regulation of E2F-4 transcriptional activity, but also to suppression of the ability of E2F-4 to transform an immortalized rodent cell line.

Adenovirus E2 Proteins↗
PubMed1994

A functional test for maternally inherited cadherin in Xenopus shows its importance in cell adhesion at the blastula stage.

We report here on the consequences of reducing the expression of EP-cadherin at the earliest stages of Xenopus development. Injection of oligodeoxynucleotides antisense to maternal EP-cadherin mRNA into full-grown oocytes reduced the mRNA level in oocytes, and the protein level in blastulae. Adhesion between blastomeres was significantly reduced, as seen in whole embryos, and in assays of the ability of blastomeres to reaggregate in culture. This effect was especially conspicuous in the inner cells of the blastula and included the disruption of the blastocoel. The severity of the EP-cadherin mRNA depletion and of the disaggregation phenotype was dose dependent. This phenotype was rescued by the injection into EP-cadherin mRNA-depleted oocytes of the mRNA coding for a related cadherin, E-cadherin, that is normally expressed at the gastrula stage in the embryonic ectoderm.

Animals↗
PubMed1992

Identification of a minimal transforming domain of p53: negative dominance through abrogation of sequence-specific DNA binding.

Mutations in the p53 gene are most frequent in cancer. Many p53 mutants possess transforming activity in vitro. In cells transformed by such mutants, the mutant protein is oligomerized with endogenous cell p53. To determine the relevance of oligomerization for transformation, miniproteins containing C-terminal portions of p53 were generated. These miniproteins, although carrying no point mutation, transformed at least as efficiently as full-length mutant p53. Transforming activity was coupled with the ability to oligomerize with wild-type p53, as well as with the ability to abrogate sequence-specific DNA binding by coexpressed wild-type p53. These findings suggest that p53-mediated transformation may operate through a dominant negative mechanism, involving the generation of DNA binding-incompetent oligomers.

Animals↗
PubMed1992

Partner support, psychological treatment, and nicotine gum in smoking treatment: an incremental study.

Smokers (N = 99) were randomly assigned to one of three conditions: nicotine gum (NG), nicotine gum plus psychological treatment (NG-PT), and nicotine gum plus psychological treatment and partner support (NG-PT-PS). Data were collected at Weeks 0, 4, 12, 26, and 52 from study start. Contrary to expectations, NG-PT-PS and NG-PT failed to increase abstinence rates. Subjects who were closer to their support partners had significantly lower abstinence rates with NG-PT-PS than with the other conditions, although not significantly at Weeks 26 and 52. Treatments without partner participation (NG-PT and NG) were significantly more effective for subjects who had an extremely close support partner outside the treatment setting than for those who did not at all weeks. The role of social support in smoking treatment is discussed.

Adult↗
PubMed1991

Wild-type p53 can down-modulate the activity of various promoters.

The wild-type (wt) p53 protein is the product of a tumor suppressor gene that is a frequent target for inactivation in many types of tumors. The nuclear localization of the protein, as well as additional features, suggest that it may be involved in the regulation of gene expression. To explore this possibility, the effects of overproduced wt p53 were investigated in a number of systems. Induction of growth arrest via the antiproliferative effect of wt p53 greatly impaired the ability of cells to exhibit an increase in c-fos mRNA upon serum stimulation. Experiments in which cells were cotransfected with p53 expression plasmids together with a reporter gene linked to various promoters revealed that wt p53 could effectively reduce transcription from a series of promoters derived from serum-inducible genes, but not from a major histocompatibility complex gene. The p53-mediated repression of c-fos gene expression occurred even in the presence of cycloheximide. Kinetic studies indicate that the effect of wt p53 is rapid, rather than representing a secondary consequence of growth arrest. These findings support a role for p53 in transcriptional regulation, perhaps by reducing the expression of genes that are needed for ongoing cell proliferation.

Animals↗
PubMed1991

Partner interaction and smoking cessation: a pilot study.

This was an exploratory study of precessation interaction between 21 smokers and their partners enrolled in a partner support smoking treatment program. The aim was to identify the partner interactions and proposed quitting strategies that were associated with cessation. Significant results (p less than .05) and trends (p less than .10) were reported. Both smoker and partner interactions predicted cessation. Failure to quit was predicted by smokers' negative behavior (prosmoking statements, interrupting the partner, and criticism/rejection of help) and by partners' suggestion to disengage from the quitting process. Partner's suggestion to disengage may be a reaction to the smokers' negative behavior because it was positively correlated with it. Successful quitters and their partners proposed more self-help strategies than did nonquitters and their partners. Nonquitters proposed more cooperative strategies than did successful quitters. Thus, suggesting strategies that encourage autonomy and self-mastery, rather than dependence on another person, may lead to more positive outcomes.

Adult↗
PubMed1991

Urinary tract stones: a complication of the Kock pouch continent urinary diversion.

Urinary tract stone disease has been found to be a later complication associated with the construction of the Kock pouch continent urinary diversion. Of 383 patients who underwent Kock pouch diversion between August 1982 and December 1986 stones developed in the pouch in 64 (16.7%), usually on exposed staples or eroded Marlex used to construct the nipple valves. Stones have recurred in 13 of the 64 patients (22%). Most stones were removed endoscopically with techniques similar to those used for percutaneous stone removal. Risk factors for stone formation include Marlex collar erosion and acute pyelonephritis. Changes in surgical techniques with elimination of the Marlex collar and a reduction in the number of staples have reduced the incidence of this later complication to 10%.

Female↗
PubMed1991

Induction of growth arrest by a temperature-sensitive p53 mutant is correlated with increased nuclear localization and decreased stability of the protein.

A temperature-sensitive mutant of p53, p53Val-135, was found to be able to arrest cell proliferation when overexpressed at 32.5 degrees C. While much of the protein was cytoplasmic in cells proliferating at 37.5 degrees C, it became predominantly nuclear at 32.5 degrees C. Concomitantly, p53Val-135 became destabilized, although not to the extent seen in primary fibroblasts.

Animals↗
PubMed1991

Expression of a novel cadherin (EP-cadherin) in unfertilized eggs and early Xenopus embryos.

Two distinct cadherin cDNA clones of Xenopus laevis were isolated from a stage 17 embryo cDNA library. Analysis of the complete deduced amino acid sequences indicated that one of these molecules is closely homologous to chicken and mouse N-cadherin, while the other displays comparable homology to both E- and P-cadherins and was thus denoted EP-cadherin. This molecule has an apparent relative molecular mass of 125 x 10(3) (compared to approx. 138 x 10(3) or approx. 140 x 10(3) of E-cadherin and N-cadherins, respectively). Northern and Western blot analyses indicated that N-cadherin is first expressed at the neurula stage while EP-cadherin is the only cadherin detected in unfertilized eggs and cleavage stage embryos. Immunolabeling of Xenopus eggs with antibodies prepared against a fusion protein, containing a segment of EP-cadherin, indicated that the protein is highly enriched at the periphery of the animal hemisphere. EP-cadherin was also found in A6 epithelial cells derived from Xenopus kidneys, and was apparently localized in the intercellular adherens junctions.

Amino Acid Sequence↗
PubMed1991

EP-cadherin in muscles and epithelia of Xenopus laevis embryos.

EP-cadherin is a novel Xenopus Ca+2-dependent adhesion molecule, which shares comparable homology with mouse E- and P-cadherins (Ginsberg, De Simone and Geiger; 1991, Development 111, 315-325). We report here the patterns of expression of this molecule in Xenopus laevis embryos at different developmental stages ranging from cleavage to postmetamorphic. EP-cadherin is already expressed in the oocyte and egg and can then be detected in close association with the membrane of all blastomeres up to late blastula stages. Starting at late gastrula stages, the level of EP-cadherin expression increases sharply in non-neural ectodermal cells, in the somites and in the notochord; it persists in endodermal cells and decreases rapidly in all migratory cells. During neurulation the level of EP-cadherin expression declines gradually in the nervous system and is undetectable here throughout later development except in the optic nerve and in the neural part of the olfactory organ. This pattern continues during later development so that in the tailbud stage and up to metamorphosis the most prominent staining is detected in the epidermis and skeletal muscle. After metamorphosis, the molecule gradually disappears from the muscle tissue and the major site of expression remains the skin. EP-cadherin is invariably present in close association with the cell membrane. In the muscle it is associated with the sarcolemma at regions of myoblast-myoblast or myotube-myotube contact. In epidermal cells, EP-cadherin is usually coexpressed with E-cadherin. Yet, while E-cadherin staining is always restricted to the basolateral aspects of the cells, EP-cadherin is often distributed throughout the plasmalemma including the apical surface.

Animals↗
PubMed1991

Transfected mouse c-jun can inhibit transformation of primary rat embryo fibroblasts.

The c-jun gene, which encodes a transcriptional regulatory protein, is the cellular homologue of the transforming gene of avian sarcoma virus 17. In an attempt to assess the biological activities of mouse c-jun, we studied the consequences of its overproduction in an in vitro transformation assay. A c-jun expression plasmid failed to cooperate with either ras, myc or mutant p53 in this focus formation assay. On the other hand, it dramatically inhibited the ability of various oncogene combinations to elicit foci upon transfection into primary rat embryo fibroblasts. Deletion plasmids lacking either the transactivating domain or the leucine repeat of c-jun still displayed a pronounced inhibitory activity. On the contrary, a plasmid encoding only the first 187 amino acids of c-jun had no such activity. The data suggests that enhanced c-jun expression may interfere with the induction or proliferation of transformed cells in this system, and that the inhibitory activity resides in the C-terminal half of the molecule.

Animals↗
PubMed1990

Broad spectrum pan-cadherin antibodies, reactive with the C-terminal 24 amino acid residues of N-cadherin.

We describe here the preparation and application of antibodies directed against a synthetic, 24 amino acid long, peptide corresponding to the conserved cytoplasmic C terminus of N-cadherin. We demonstrate here that the antibodies to the synthetic peptide react extensively with all known members of the cadherin family and, in addition, recognize novel cadherins in a variety of cells and tissues, suggesting that these antibodies indeed exhibit pan-cadherin reactivity. By Western blot screening of chicken tissues at least 4 different immunoreactive bands were resolved, commonly disclosing 2-3 distinct bands within the same tissue. The pan-cadherin antibodies also displayed a broad interspecies cross reactivity, recognizing cadherins in man, bovine, canine, avian, amphibian and teleost cells. This property renders these antibodies excellent reagents for the cloning and identification of novel cadherins. Immunocytochemical labelling with the pan-cadherin antibodies, at the light- and electron-microscope levels, revealed an extensive reactivity with intercellular adherens junctions in cardiac muscle and in various epithelia. We thus propose that the pan-cadherin antibodies may be used as ubiquitous cadherin probes and serve as markers for adherens junctions.

Amino Acid Sequence↗
PubMed1990

Protein-binding elements in the promoter region of the mouse p53 gene.

p53 is a cellular protein whose expression plays a crucial role in the regulation of cell proliferation and of neoplastic processes. p53 mRNA levels in mouse fibroblasts can be elevated in response to TPA and to serum stimulation. The promoter region of the p53 gene contains a conserved element which is highly homologous to the consensus AP1 binding site (7/8 matching bases). This AP1-like site, denoted the PF1 site, confers upon a heterologous promoter ability to respond to elevated expression of c-jun. Furthermore, the PF1 site binds protein(s) in a specific and serum-induced manner. Unexpectedly, this factor is most probably not AP1, as evident from the inability of an authentic AP1 site to compete the binding efficiently, as well as from the failure of purified AP1 to bind to the PF1 site. Hence, PF1 may be a novel AP1-related transcription factor. In addition, the 5' region of the p53 gene also contains an NF1 binding site, whose location suggests a possible regulatory role.

Animals↗