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S Carrère

Publications and source records attributed to S Carrère.

14 recordsLinked to original sources
PubMed2001

Identification of amino acid residues in the ETS transcription factor Erg that mediate Erg-Jun/Fos-DNA ternary complex formation.

Jun, Fos, and Ets proteins belong to distinct families of transcription factors that target specific DNA elements often found jointly in gene promoters. Physical and functional interactions between these families play important roles in modulating gene expression. Previous studies have demonstrated a direct interaction between the DNA-binding domains of the two partners. However, the molecular details of the interactions have not been investigated so far. Here we used the known three-dimensional structures of the ETS DNA-binding domain and Jun/Fos heterodimer to model an ETS-Jun/Fos-DNA ternary complex. Docking procedures suggested that certain ETS domain residues in the DNA recognition helix alpha3 interact with the N-terminal basic domain of Jun. To support the model, different Erg ETS domain mutants were obtained by deletion or by single amino acid substitutions and were tested for their ability to mediate DNA binding, Erg-Jun/Fos complex formation, and transcriptional activation. We identified point mutations that affect both the DNA binding properties of Erg and its physical interaction with Jun (R367K), as well as mutations that essentially prevent transcriptional synergy with the Jun/Fos heterodimer (Y371V). These results provide a framework of the ETS/bZIP interaction linked to the manifestation of functional activity in gene regulation.

Amino Acid Sequence↗
PubMed2001

Synergistic induction of matrix metalloproteinase 1 by interleukin-1alpha and oncostatin M in human chondrocytes involves signal transducer and activator of transcription and activator protein 1 transcription factors via a novel mechanism.

OBJECTIVE: To investigate the mechanism of interleukin-1alpha (IL-1alpha) and oncostatin M (OSM) synergistic regulation of matrix metalloproteinase 1 (MMP-1) in human chondrocytes. METHODS: Using an immortalized human chondrocyte cell line (T/C28a4), we investigated regulation of the MMP-1 gene. Northern blotting and flow cytometric analysis were used to assess changes in receptor, MMP-1, and c-fos expression. Transient transfections using MMP-1 promoter/luciferase constructs, electrophoretic mobility shift assay, and site-directed mutagenesis were used to investigate MMP-1 promoter activation. RESULTS: We found no alteration in the expression of receptors used by these cytokines after stimulation with IL-1alpha/OSM. Using MMP-1 promoter/luciferase reporter constructs, we found that the proximal (-517/+63) region of the MMP-1 promoter was sufficient to support a synergistic activation. A role for activated signal transducers and activators of transcription (STAT-3) was demonstrated, although no binding of STAT-3 to the MMP-1 promoter was found. However, constitutive binding of activator protein 1 (AP-1) was detected, and changes in c-fos expression could modulate promoter activity. CONCLUSION: Since no changes in receptor expression were observed, receptor modulation cannot account for the IL-1alpha/OSM synergy observed. Instead, the interplay of various intracellular signaling pathways is a more likely explanation. STAT activation is required, but STAT proteins do not interact directly with the MMP-1 promoter. We propose that activated STATs stimulate c-fos expression, and changes in expression of the AP-1 components regulate MMP-1 expression. We highlight a new mechanism for MMP-1 regulation in human chondrocytes that could provide potential new therapeutic targets.

Cell Line, Transformed↗
PubMed2001

Esculetin inhibits cartilage resorption induced by interleukin 1alpha in combination with oncostatin M.

OBJECTIVE: To determine if a new inhibitor, esculetin (EST), can block resorption of cartilage. METHODS: Interleukin 1alpha (IL1alpha, 0.04-5 ng/ml) and oncostatin M (OSM, 0.4-50 ng/ml) were used to stimulate the release of proteoglycan and collagen from bovine nasal cartilage and human articular cartilage in explant culture. Proteoglycan and collagen loss were assessed by dimethylmethylene blue and hydroxyproline assays, respectively. Collagenase levels were measured by assay of bioactivity and by enzyme linked immunosorbent assay (ELISA). The effects of EST on the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the transformed human chondrocyte cell line T/C28a4 were assessed by northern blot analysis. TIMP-1 protein levels were assayed by ELISA. The effect of EST on the MMP-1 promoter was assessed using a promoter-luciferase construct in transient transfection studies. RESULTS: EST inhibited proteoglycan and collagen resorption in a dose dependent manner with significant decreases seen at 66 microM and 100 microM EST, respectively. Collagenolytic activity was significantly decreased in bovine nasal cartilage cultures. In human articular cartilage, EST also inhibited IL1alpha + OSM stimulated resorption and decreased MMP-1 levels. TIMP-1 levels were not altered compared with controls. In T/C28a4 chondrocytes the IL1alpha + OSM induced expression of MMP-1, MMP-3, and MMP-13 mRNA was reduced to control levels by 250 microM EST. TIMP-1 mRNA levels were unaffected by EST treatment. All cytokine stimulation of an MMP-1 luciferase-promoter construct was lost in the presence of the inhibitor. CONCLUSION: EST inhibits degradation of bovine nasal cartilage and human articular cartilage stimulated to resorb with IL1alpha + OSM.

Animals↗
PubMed2000

Predicting marital stability and divorce in newlywed couples.

A longitudinal study with 95 newlywed couples examined the power of the Oral History Interview to predict stable marital relationships and divorce. A principal-components analysis of the interview with the couples (Time 1) identified a latent variable, perceived marital bond, that was significant in predicting which couples would remain married or divorce within the first 5 years of their marriage. A discriminant function analysis of the newlywed oral history data predicted, with 87.4% accuracy, those couples whose marriages remained intact or broke up at the Time 2 data collection point. The oral history data predicted with 81% accuracy those couples who remained married or divorced at the Time 3 data collection point. This study offers support for causal linkages between perceptual biases and selective attention on the path of marriage.

Adult↗
PubMed2000

The baby and the marriage: identifying factors that buffer against decline in marital satisfaction after the first baby arrives.

This longitudinal study identified factors of couples' marital friendship in the beginning months of marriage that predicted stability versus decline in marital satisfaction over the transition to parenthood. Newlywed couples (N = 130) were followed longitudinally for 6 years. Forty-three couples because parents, and 39 childless couples served as a control group. Couples were interviewed about the history and philosophy of their relationship as newlyweds. What predicted the stable or increasing marital satisfaction of mothers were the husband's expression of fondness toward her, the husband's high awareness for her and their relationship, and her awareness for her husband and their relationship. In contrast, what predicted the decline in marital satisfaction of mothers were the husband's negativity toward his wife, the husband's disappointment in the marriage, or the husband or wife having described their lives as chaotic.

Adult↗
PubMed1999

Predicting divorce among newlyweds from the first three minutes of a marital conflict discussion.

This study tested the hypothesis that how a discussion of a marital conflict begins--in its first few minutes--is a predictor of divorce. The marital conflict discussion of 124 newlywed couples was coded using the Specific Affect Coding System, and the data were divided into positive, negative, and positive-minus-negative affect totals for five 3-minute intervals. It was possible to predict marital outcome over a 6-year period using just the first 3 minutes of data for both husbands and wives. For husbands this prediction improved as the groups diverged in the remaining 12 minutes; for wives the prediction remained equally powerful for the remaining 12 minutes as it had been in the first 3 minutes.

Adult↗
PubMed1998

Erg proteins, transcription factors of the Ets family, form homo, heterodimers and ternary complexes via two distinct domains.

The ets genes family encodes a group of proteins which function as transcription factors under physiological conditions. We report here that the Erg proteins, members of the Ets family, form homo and heterodimeric complexes in vitro. We demonstrate that the Ergp55 protein isoform forms dimers with itself and with the two other isoforms, Ergp49 and Ergp38. Using a set of Erg protein deletion mutants, we define two distinct domains independently involved in dimerization. The first one is located in the amino-terminal part of the protein containing the pointed domain (PNT), conserved in a subset of Ets proteins. The second one resides within the ETS domain, the DNA-binding domain. We also show that the Erg protein central region behaves as an inhibitory domain of dimerization and its removal enhances the Ergp55 transactivation properties. Furthermore, Ergp55 forms heterodimers with some other Ets proteins. Among the latter, we show that Fli-1, Ets-2, Er81 and Pu-1 physically interact with Erg. Finally, we show that the formation of the previously described ternary complex Ergp55/Fos/jun is mediated by ETS domain and Jun protein, while the ternary complex Ergp49/Fos/Jun is mediated by Fos protein.

Binding Sites↗
PubMed1996

Erg, an Ets-family member, differentially regulates human collagenase1 (MMP1) and stromelysin1 (MMP3) gene expression by physically interacting with the Fos/Jun complex.

Collagenase1 (MMP1) and stromelysin1 (MMP3) are extracellular proteolytic enzymes that degrade connective tissue macromolecules and basement membranes. Both genes are regulated by the Ets and Fos/Jun families of transcription factors/oncoproteins. Here, we show that two members of the Ets-family, Ets2 and Erg and their combinations differentially regulate collagenase1 and stromelysin1 promoter activity. In transiently transfected cells, Ets2 activates both promoters whereas Erg induces collagenase1 but not stromelysin1 promoter activity. Moreover, Erg completely inhibits stromelysin1 promoter activation by Ets2. In gel shift assays however, the Erg protein bound little or not to the collagenase1 promoter, whereas it bound to the stromelysin1 promoter. By site-specific mutagenesis, we identified one major site at -88 that abolished collagenase1 promoter activation by Erg. Surprisingly, mutation of the collagenase1 AP1 site at -73 also abolished the activation by Erg suggesting that Erg cooperates with Fos/Jun in collagenase1 promoter regulation. Indeed, gel shift and in vitro protein interaction studies showed that Erg binds to the Fos/Jun complex. Thus, Erg represents the first example of a transcription factor that can distinguish between the collagenase1 and stromelysin1 promoters in that when Erg is recruited by Fos/Jun at the promoter, it transcriptionally activates collagenase1 gene but not stromelysin1 expression.

Binding Sites↗
PubMed1991

Traffic congestion, perceived control, and psychophysiological stress among urban bus drivers.

The operation of public transit vehicles in urban centers is a highly stressful job. There has been, however, little detailed analysis of what specific characteristics of the psychosocial or physical job environmental of public transit operators contribute to the high levels of job stress associated with this occupation. In the present study, we show a high degree of association between exposure to peak traffic conditions and on-the-job elevations of urinary catecholamines. These significant relations remain after incorporating various controls for possible selection factors (e.g., job seniority) and health-relevant parameters (e.g., age, smoking). Furthermore, we show that reductions in perceived control on the job partially account for the linkages between traffic congestion and psychophysiological stress.

Adult↗
PubMed1981

[Eruptive generalized syringomas, milium and atrophoderma vermiculata. Nicolau and Balus' syndrome (author's transl)].

It appears justified to isolate under the term syndrome of Nicolau and Balus', a group of deformities that include eruptive syringomas of the disseminated micropapular type, milium cysts and atrophoderma vermiculata. We present here a highly typical observation of an 11-year-old child whose mother also presented with eruptive syringomas. This syndrome accentuates the semiological value of disseminated syringomas and atrophoderma vermiculata, which often occur in the context of a complex syndrome. In addition, an associated elastopathy was discovered by light- and electron-microscopic observations.

Adenoma↗
PubMed1978

[Comel's linear circumflex ichthyosis and Netherton's syndrome. General conceptions based on study of 4 cases (author's transl)].

We have recently observed 4 new particularly demonstrative cases and we think it is adequate to give a general conception in order to bring together in one and a single syndrom the ichthyosis linearis circumflexa Comel and the Netherton's syndrom. We also emphasize some features:--the possible association of ichthyosis linearis circumflexa with family epileptogenous encephalopathy;--a particular type of trichorrhexis which we named "frayed pili torti";--the usual lethality in males, with possible serious viral and pyococcic superinfection;--the characteristics of ichtyosiform erythroderma in the Netherton's syndrom. At the end of this study we confirm that a unicist theory which would consider Netherton's syndrom and ichthyosis linearis circumflexa as one and a single disease should be adopted.

Adult↗