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H van Dam

Publications and source records attributed to H van Dam.

32 records · Page 2Linked to original sources
PubMed1993

Heterodimer formation of cJun and ATF-2 is responsible for induction of c-jun by the 243 amino acid adenovirus E1A protein.

The adenovirus E1A proteins differentially regulate AP-1-responsive genes. Collagenase and stromelysin are repressed by E1A, whereas the expression of c-jun is elevated. Inhibition of collagenase has been found to be exerted through the consensus AP-1 binding site TGAGTCA. Here we show that the distal AP-1 binding site in the c-jun promoter, the jun2TRE (TTACCTCA), is the decisive element of this promoter in mediating the positive response to the 243 amino acid E1A product. In vitro binding studies revealed that, in contrast to the consensus AP-1 site which is preferentially targeted by dimers composed of the Jun and Fos families, the jun2TRE binds heterodimers composed of cJun and ATF-2(-like) proteins. Since stimulation of c-jun transcription is a function of the transforming domain of E1A encoded by conserved region 1, cJun--ATF-2 may be one of the effector factors involved in transformation. The data further suggest that E1A can distinguish between cJun--cJun and cJun--ATF-2 in imposing opposite states of activity.

3T3 Cells↗
PubMed1993

Increased cyclin A and decreased cyclin D levels in adenovirus 5 E1A-transformed rodent cell lines.

Adenovirus-(Ad)- E1A proteins carry two conserved domains (CR1 and CR2) required for transformation of primary rodent cells and essential for association with cellular proteins, including p105RB, p58cyclin A and p33cdk2. We show that in normal rat kidney 49F (NRK) cell lines expressing various mutant Ad5-E1A genes, CR2-, but not CR-1-, deletion mutants induce a typical transformed phenotype as characterized by morphology, absence of density arrest and loss of serum requirement. This indicates that induction of these transformed properties is a function of CR1. The fact that E1A proteins with deletions in CR2 show a greatly reduced association with RB, cyclin A and p33cdk2 suggests that these associations are dispensable for E1A-mediated transformation of NRK cells. Induction of the transformed properties is accompanied by a CR1-dependent increase in Proliferating Cell Nuclear Antigen and cyclin A gene expression. Elevated mRNA and protein levels of cyclin A were also found in Ad12-E1-transformed NRK cells but not in ras-transformed NRK cells. On the other hand, cyclin D expression is decreased in a CR1-dependent manner. Although Ad5-E1A proteins are sufficient to transform NRK cells, further deregulation of growth is obtained when Ad5-E1B proteins are co-expressed. One of the Ad5-E1B effects is the sequestration of the p53 protein into a cytoplasmic body containing the p53/Ad5-E1B-55 kD complex. Interestingly, in NRK cell lines expressing Ad5-E1B-55 kD, cyclin A could be detected not only in the nucleus but also in the cytoplasmic bodies. These results indicate that the deregulation of cell cycle control by the Adenovirus-E1 region may be due to a CR1-dependent alteration of the expression of cyclins A and D.

Adenovirus E1A Proteins↗
PubMed1992

Improvement of breeding success of the moor frog (Rana arvalis) by liming of acid moorland pools and the consequences of liming for water chemistry and diatoms.

Liming experiments with powdered limestone (grain size < 3 mm) were conducted in eight acid shallow moorland pools in the Tongerense Heide heathland area from February 1988 until November 1989. The effects on water chemistry, diatoms and fungal infection of the eggs of the moor frog were studied. After an initial treatment in March 1988, the pH increased from c. 4.0 to c. 5.0 in those pools which dried out in summer and to c. 6.0 in the permanent pools. Alkalinity increased from 0 to 20-200 microeq litre(-1) in temporary pools and from 0 to 300-500 microeq litre(-1) in permanent pools. As drying out of the pools caused reacidification, after refilling the temporary pools were relimed in March 1989. No significant changes were found in concentrations of phosphate and nitrogen compounds. Eunotia paludosa, which is characteristic for ologotrophic, very acid pools and bogs with a fluctuating water table, was the dominant diatom in the untreated pools. It was replaced by eutraphentic and saprophilous taxa, particularly in the permanent pools. Species from extremely soft waters, which are very sensitive to acidification, were found only occasionally in some samples from the treated permanent pools. After liming the proportion of infected moor frog eggs decreased from c. 95% in the untreated to c. 5% in the treated pools.

Journal Article↗
PubMed1992

Ultraviolet-radiation induced c-jun gene transcription: two AP-1 like binding sites mediate the response.

In HeLa cells transcription of the c-jun gene is activated strongly and rapidly by ultraviolet (UV) irradiation and, to a somewhat lesser extent, by treatment with phorbol ester tumor promoters. In the same cells UV and phorbol esters only marginally enhance the abundance of RNA transcribed from the jun D gene and from the gene coding for the serum response factor (which in turn acts on the UV and phorbol ester response element of the c-fos gene). In contrast to c-jun, jun B transcription is induced more efficiently by phorbol ester than by UV irradiation, suggesting that the members of the jun family are differently regulated. The promoter of c-jun carries two enhancer elements resembling AP-1 binding sites: the jun1 UV response element (URE-71 TGACATCA -64) and the jun2 URE (-190 TTACCTCA-183). These elements act independently in the UV induced expression of c-jun. In the context of the complete c-jun promoter they seem not to be required for c-jun induction by phorbol esters. When fused to the Herpes simplex thymidine kinase promoter, however, the isolated elements mediate induction by both UV and phorbol esters. UV and phorbol ester treatment of cells increases the binding of transcription factors to both elements. Both elements bind factors different in modification or/and constitution from AP-1, the heterodimeric transcription factor composed of c-Fos and c-Jun that controls the activity of the UV and phorbol ester response element (-72 TGAGTCA-66) of the human collagenase gene.

Base Sequence↗
PubMed1991

Co-regulated expression of junB and MHC class I genes in adenovirus-transformed cells.

The expression of the junB gene parallels the expression of the MHC class I genes in Adenovirus (Ad) transformed cells. In Ad12E1-transformed primary BRK cells both genes are transcriptionally repressed only when the 13S product of Ad12E1A is present. This indicates that repression of MHC class I and junB genes is a function of conserved region 3 (CR3) of the Ad12E1A protein. In Ad5-transformed BRK cells expression of these genes is unchanged. In established NRK cells, however, introduction of Ad12E1A does not cause repression of the MHC class I and junB genes, but in these cells Ad5E1A increases the expression of both MHC class I and junB. Using mutant Ad5E1A genes, it is shown that this activation is mediated by CR1. Introduction of a functional junB gene under the control of a heterologous promoter in Ad12E1-transformed BRK cells causes no increase in MHC class I expression. This demonstrates that the down-regulation of junB is not directly responsible for class I repression, but rather that both genes are coregulated by the Ad12E1 region.

Adenoviruses, Human↗
PubMed1990

A novel function of the transforming domain of E1a: repression of AP-1 activity.

Adenovirus E1a represses transcription of the collagenase gene via the phorbol ester-responsive element (collTRE). The mechanism involves inhibition of the trans-activating function of the transcription factor AP-1 without reduction of its synthesis and without any apparent change in DNA binding or composition. The ability of E1a to downmodulate AP-1 is a unique property among dominant oncogenes. This repression depends on conserved region 1, one of the transforming domains of E1a, indicating that it is an integral feature of adenovirus transformation.

Adenovirus Early Proteins↗
PubMed1990

Differential effects of the adenovirus E1A oncogene on members of the AP-1 transcription factor family.

The adenovirus early region 1A (E1A) oncogene interferes with the expression level and activity of the AP-1 transcription factor family. E1A abolished the transactivating function of AP-1 (Jun/Fos), which binds to the 12-O-tetradecanoylphorbol-13-acetate-responsive element of the collagenase gene (collTRE). In contrast, the activity of another member of the AP-1 family that binds to the c-junTRE was not repressed. The mRNA expression of the c-jun gene was, in fact, strongly elevated in various cell types expressing the E1A gene of either adenovirus type 5 (Ad5) or Ad12. The regulation of the junB gene by adenovirus E1A, on the other hand, depended both on the cell type and on the transforming adenovirus serotype. The fact that E1A-induced alterations in the repertoire of AP-1 transcription factors depend on its transforming domain in conserved region 1 suggests that the effects are relevant for the transformation process.

Adenovirus Early Proteins↗
PubMed1989

Adenovirus E1A represses transcription of the cellular JE gene.

The expression of the growth factor-inducible JE gene was severely reduced in cells expressing region E1A of human adenoviruses. This reduction was not caused by a decreased stability of JE mRNA but by a reduced transcription rate as determined by run-on transcription experiments. Nevertheless, JE mRNA could still be induced by growth factors, suggesting that intracellular signaling is not blocked but rather that the basal level of JE transcription is repressed by E1A.

Adenovirus Early Proteins↗
PubMed1989

DNA-binding domain of human c-Myc produced in Escherichia coli.

We have identified the domain of the human c-myc protein (c-Myc) produced in Escherichia coli that is responsible for the ability of the protein to bind sequence-nonspecific DNA. Using analysis of binding of DNA by proteins transferred to nitrocellulose, DNA-cellulose chromatography, and a nitrocellulose filter binding assay, we examined the binding properties of c-Myc peptides generated by cyanogen bromide cleavage, of mutant c-Myc, and of proteins that fuse portions of c-Myc to staphylococcal protein A. The results of these analyses indicated that c-Myc amino acids 265 to 318 were responsible for DNA binding and that other regions of the protein (including a highly conserved basic region and a region containing the leucine zipper motif) were not required. Some mutant c-Mycs that did not bind DNA maintained rat embryo cell-cotransforming activity, which indicated that the c-Myc property of in vitro DNA binding was not essential for this activity. These mutants, however, were unable to transform established rat fibroblasts (Rat-1a cells) that were susceptible to transformation by wild-type c-Myc, although this lack of activity may not have been due to their inability to bind DNA.

Amino Acid Sequence↗
PubMed1989

The repression of the growth factor-inducible genes JE, c-myc and stromelysin by adenovirus E1A is mediated by conserved region 1.

The growth factor-inducible cellular genes JE, c-myc and stromelysin (sml) are strongly repressed upon transformation by adenovirus E1A. As E1A proteins are multifunctional and apparently contain distinct domains (conserved regions 1, 2 and 3), each with a specific effect on gene regulation and cell-transformation, we have investigated which of the three conserved regions are responsible for the reduced expression of these genes. To this end, we monitored the expression of the JE, sml and c-myc genes in a panel of normal rat kidney (NRK) cells expressing different mutant E1A genes. Only CR1, and not CR2 or CR3 were found to be essential for the repression of the genes, indicating that CR1, one of the regions essential for cell transformation, represents an autonomous gene regulatory function that can operate in the absence of CR2. We also show that the association of E1A proteins to a 300 kD cellular protein in NRK cells coincides with the ability to repress these genes.

Adenovirus Early Proteins↗
PubMed1987

Countertransference during an analyst's brief illness.

This paper describes an example of acting out of countertransference during a brief but unexpected serious illness. My emphasis is on the regression that occurred with hospitalization and how it dovetailed with a particular patient's transference. A confluence of my residual neurosis, the patient's neurosis, her transference state, her other characteristics (that she was female, for example), plus the fact that she was the last patient contacted, all conspired with the regression from the trauma of being hospitalized to produce the countertransference reaction. This presentation is also intended to add to the very sparse literature on a distasteful subject of supreme importance.

Countertransference↗
PubMed1980

Ultraviolet photoelectron spectroscopy of cyclic amidines. 2. Electronic structure of clonidine and some related 2-(phenylimino)imidazolidines with alpha-adrenergic activity.

Ultraviolet photoelectron spectroscopy (UV PES) and CNDO/s molecular orbital calculations have been employed to investigate the electronic structure of clonidine and some other 2-(phenylimino)imidazolidines. The assignment of the bands in the spectra to particular molecular orbitals is based on the CNDO/s results in conjunction with Koopmans' theorem, substituent effects, and differences in intensity between the He (I) and He(II) spectra. The location of the energy levels of orbitals with mainly nN and delta character is not correctly estimated estimated by CNDO/s, while the pi orbital energy levels are satisfactorally predicted. The UV PES and CNDO/s results indicate in contrast investigated 2-(phenylimino)imidazolidines, which may indicate that differences in hypotensive activity cannot be ascribed to variations in steric hindrance within the molecules. The first ionization energies of the pharmacologically active 20-(phenylimino)imidazolidines do not correlate with hypotensive activity based on dosage data after intravenous administration to rats.

Adrenergic alpha-Antagonists↗