Biomedical subjects

C Gélinas

Publications and source records attributed to C Gélinas.

7 recordsLinked to original sources

PubMed1992

The RxxRxRxxC motif conserved in all Rel/kappa B proteins is essential for the DNA-binding activity and redox regulation of the v-Rel oncoprotein.

The v- and c-Rel oncoproteins bind to oligonucleotides containing kappa B motifs, form heterodimers with other members of the Rel family, and modulate expression of genes linked to kappa B motifs. Here, we report that the RxxRxRxxC motif conserved in all Rel/kappa B family proteins is absolutely required for v-Rel protein-DNA contact and its resulting transforming activity. We also demonstrate that serine substitution of the cysteine residue conserved within this motif enables v-Rel to escape redox control, thereby promoting overall DNA binding. These mutant proteins retained the ability to competitively inhibit kappa B-mediated transcriptional activation of the human immunodeficiency virus long terminal repeat but failed to efficiently transform chicken lymphoid cells both in vitro and in vivo. Our data indicate that reduction of the conserved cysteine residue in the RxxRxRxxC motif may be required for optimal DNA-protein interactions. These results provide direct biochemical evidence that the DNA-binding activity of v-Rel is subject to redox control and that the conserved cysteine residue in the RxxRxRxxC motif is critical for this regulation. These studies suggest that the DNA-binding, transcriptional, and biological activities of Rel family proteins may also be subject to redox control in vivo.

Base Sequence↗

PubMed1992

Transcriptional activity of rel family proteins.

Our studies originally demonstrated that the v-rel oncoprotein repressed gene expression in chicken lymphoid cells, while it activated transcription in rodent fibroblasts. Here we report that the c-rel protein can activate expression of genes linked to kappa B motifs when low levels of endogenous kappa B-binding activity are present. In contrast v-rel, and to a lesser extent c-rel, inhibit NF-kappa B-mediated activation of the human immunodeficiency virus long terminal repeat (HIV LTR) in phorbol ester-stimulated HeLa cells. Competition assays show that v-rel competitively inhibits both NF-kappa B and c-rel-mediated transcriptional activation. Analysis of mutant HIV LTR-chloramphenicol acetyltransferase (CAT) constructs in which all Sp1 or both NF-kappa B elements have been deleted shows that NF-kappa B motifs are required for rel-mediated effects on gene expression. Transforming v-rel mutants compete efficiently with phorbol ester-activated kappa B factors, whereas a transformation-defective mutant of v-rel is impaired in this activity. Taken together, these results strengthen the hypothesis that v-rel functions as a dominant interfering member of rel family proteins. These results also suggest that the ability of v- and c-rel to activate or repress gene expression in specific cells may result from their capacity to compete with endogenous rel family proteins whose expression and/or activity are cell-specific.

Base Sequence↗

PubMed1990

Adherence of HDPE powder coating on Co-Cr surfaces: effect of substrate preparation and gas sterilization.

As part of the development of a hemiarthroplasty implant with a compliant surface layer, the effect of surface preparation of a cast Co-Cr alloy substrate on the adhesion of a polymeric coating was studied. High-density polyethylene (HDPE) coatings were deposited on Co-Cr alloys without adhesive by spraying powder onto the surface of specimens maintained at a controlled temperature. Prior to deposition, two different types of surface preparation were carried out: chemical etching and grit-blasting. Adherence tests were performed in order to study the effect of the surface preparation of a Co-Cr alloy on the adherence of the HDPE film. The etching process enhanced the adherence by a factor of 10 compared to the grit-blasting process. For coatings deposited on grit-blasted Co-Cr surfaces, rupture occurred at the interface (adhesive mode) as well as in the coating (cohesive mode). A full cohesive mode was observed for films deposited on etched surfaces. Gas sterilization with an ethylene oxide and Freon 12 solution did not change significantly the adherence of the film deposited on etched surfaces. Examination of the surfaces indicated that the etching process created a specific type of porosity consisting of dendritic cavities whereas grit-blasting produced surface irregularities. Cavities produced by etching were larger that the polymer powder particles and could be easily filled. The coating of an etched Co-Cr alloy substrate with a layer of HDPE provided an interface that could probably sustain the physiological loading in a normal synovial joint.

Biocompatible Materials↗

PubMed1988

The v-rel oncogene encodes a cell-specific transcriptional activator of certain promoters.

Transformation by the v-rel oncogene of avian reticuloendotheliosis virus strain T (Rev-T) is primarily cell-specific. While v-rel efficiently transforms chicken spleen and bone marrow stem cells in vitro and induces rapid lethal lymphomas in young birds, it does not rapidly transform chicken embryo fibroblasts. The nuclear localization of the v-rel gene product in non-transformed fibroblasts along with its ability to function as a transforming protein in the nucleus of chicken spleen cells suggests that p59v-rel might belong to the family of nuclear oncoproteins and thus may express an immortalizing function in fibroblasts. To gain insight into the specificity of cell transformation by the v-rel oncogene, we determined whether v-rel could immortalize primary rat fibroblasts. Our experiments have shown that, unlike other nuclear oncoproteins, p59v-rel did not immortalize primary rat embryo fibroblasts. However p59v-rel was able to cooperate in a synergistic way with the polyomavirus middle T protein in inducing efficient transformation of established rat fibroblasts by increasing the steady-state level of middle T RNA, indicating that p59v-rel might function as a transactivator. Cotransfection of cells from different species with the v-rel gene along with constructs expressing the chloramphenicol acetyl transferase gene under the control of different promoters revealed that p59v-rel is a cell-specific transcriptional transactivator of certain promoters. Moreover, the extent of cell-specific transactivation by v-rel correlated with its toxic effect in these same cells.

Animals↗

PubMed1986

Nondefective spleen necrosis virus-derived vectors define the upper size limit for packaging reticuloendotheliosis viruses.

We constructed a nondefective retrovirus vector based on spleen necrosis virus (SNV), a replication-competent reticuloendotheliosis virus. We introduced different DNA sequences into this vector and studied the ability of the resulting viruses to replicate in chicken embryo fibroblasts. The replication efficiency of SNV-derived viruses decreased with increasing virus size. Viruses larger than 9.4 kilobases (kb) were rapidly overgrown by replication-competent deletion mutants. The size restriction for the efficient replication of nondefective SNV-derived viruses prevented the production of viruses larger than 10.0 kb. Analysis of the kinetics of virus particle release indicated that the size restriction occurred during virus encapsidation.

Capsid↗

PubMed1985

Malignant transformation of rat cells by the polyomavirus middle T gene.

To gain an insight into the molecular mechanism of cooperation between the polyomavirus middle T gene and cellular genes in the tumorigenic process, we have examined various properties of rat cell lines transformed by middle T alone. Middle T transformants display a phenotype ranging from nontumorigenic (flat) to fully transformed (tumorigenic) and the phenotype of a given cell line correlates very well with its cellular level of middle T antigen. Highly transformed, tumorigenic variants arise spontaneously in the flat cells during their growth with a mutation rate of 2.2 X 10(-5) per cell per generation. These variants contain elevated levels of both middle T antigen and middle T transcripts, suggesting that fully transformed cells arise as a consequence of an efficient mode of viral gene expression.

Animals↗

PubMed1975

Hepatic echography.

There are 2 kinds of echographic investigations: those which are only complementary and those which are specific by themselves. To improve this latter category, we would like to emphasize two useful echographic signs. First, the attenuation sign, which indicates the fibrotic nature, therefore practically speaking, the cirrhotic nature of a diffuse echogenic pattern. Secondly, the posterior echo accumulation sign, which indicates the liquid nature, and therefore in general the cystic nature of a localized sonolucent pattern.

Carcinoma, Hepatocellular↗