Biomedical subjects

Begoña Torres

Publications and source records attributed to Begoña Torres.

5 recordsLinked to original sources

PubMed2005

Downstream regulatory element antagonist modulator regulates Ca2+ homeostasis and viability in cerebellar neurons.

The Na+/Ca2+ exchangers NCX1, NCX2, and NCX3 are vital for the control of cellular Ca2+ homeostasis. Here, we show that a doublet of downstream regulatory element sites in the promoter of the NCX3 gene mediates transcriptional repression of NCX3 by the Ca2+-modulated transcriptional repressor downstream regulatory element antagonist modulator (DREAM). Overexpression of a DREAM EF-hand mutant insensitive to Ca2+ (EFmDREAM) in hippocampus and cerebellum of transgenic mice significantly reduced NCX3 mRNA and protein levels without modifying NCX1 and NCX2 expression. Cerebellar granules from EFmDREAM transgenic mice showed increased levels of cytosolic Ca2+ and were more vulnerable to increased Ca2+ influx after partial opening of voltage-gated plasma membrane Ca2+ channels induced by increasing K+ in the culture medium but survived better in the conditions of reduced Ca2+ influx prevailing in low extracellular K+. Overexpression of NCX3 in EFmDREAM transgenic granules using a lentiviral vector restored the normal survival response to high K+ observed in wild-type granules. Thus, the downregulation of the regulator of Ca2+ homeostasis NCX3 by Ca2+-regulated DREAM is a striking example of the autoregulatory property of the Ca2+ signal in neurons.

Amino Acid Motifs↗

PubMed2004

Day-night changes in downstream regulatory element antagonist modulator/potassium channel interacting protein activity contribute to circadian gene expression in pineal gland.

The molecular mechanisms controlling the oscillatory synthesis of melatonin in rat pineal gland involve the rhythmic expression of several genes including arylalkylamine N-acetyltransferase (AA-NAT), inducible cAMP early repressor (ICER), and Fos-related antigen-2 (fra-2). Here we show that the calcium sensors downstream regulatory element antagonist modulator/potassium channel interacting protein (DREAM/KChIP)-3 and KChIP-1, -2 and -4 bind to downstream regulatory element (DRE) sites located in the regulatory regions of these genes and repress basal and induced transcription from ICER, fra-2 or AA-NAT promoters. Importantly, we demonstrate that the endogenous binding activity to DRE sites shows day-night oscillations in rat pineal gland and retina but not in the cerebellum. The peak of DRE binding activity occurs during the day period of the circadian cycle, coinciding with the lowest levels of fra-2, ICER, and AA-NAT transcripts. We show that a rapid clearance of DRE binding activity during the entry in the night period is related to changes at the posttranscriptional level of DREAM/KChIP. The circadian pattern of DREAM/KChIP activity is maintained under constant darkness, indicating that an endogenous clock controls DREAM/KChIP function. Our data suggest involvement of the family of DREAM repressors in the regulation of rhythmically expressed genes engaged in circadian rhythms.

Animals↗

PubMed2004

Aromatic metabolism versus carbon availability: the regulatory network that controls catabolism of less-preferred carbon sources in Escherichia coli.

The current knowledge on the genetics and biochemistry of the catabolism of aromatic compounds in Escherichia coli settles the basis to consider these pathways as a model system to study the complex molecular mechanisms that control the expression of the genes involved in the metabolism of less-preferred carbon sources in this paradigmatic organism. Two different levels of regulation are reviewed: (i) the specific regulatory mechanisms that drive the expression of the catabolic genes when the cognate inducer, i.e., the substrate of the pathway or an intermediate metabolite, is available, and (ii) the global or superimposed regulation that adjust the expression of the catabolic clusters to the general physiological status of the cell.

Adaptation, Physiological↗

PubMed2004

The BDNF gene: exemplifying complexity in Ca2+ -dependent gene expression.

Over the last 20 years, great effort has been made to decipher the molecular mechanisms used by cells to transform a cytosolic Ca2+ signal into specific, finely-controlled changes in gene expression. Several previous reviews addressed the variety of regulatory mechanisms that participate in Ca2+ -dependent gene expression in neurons (Carafoli et al., 2001; Mellstrom and Naranjo 2001; West et al., 2001). Nevertheless, recent discoveries have revealed new players and new interactions that tune this process. In this review, we will use the four promoters that regulate the expression of the brain-derived neurotrophic factor (BDNF) gene as a magnificent scenario in which these mechanisms intermingle to show the complexity of Ca2+ -dependent gene expression.

Animals↗

PubMed2003

A dual lethal system to enhance containment of recombinant micro-organisms.

Active containment systems based on the controlled expression of a lethal gene are designed to increase containment of recombinant micro-organisms used for environmental applications. A major drawback in containment is the existence of mutations that generate surviving cells that cease to respond to the toxic effect of the lethal function. In this work the authors have developed for the first time a strategy to reduce the problem of mutations and increase the efficiency of containment based on the combination of two lethal functions acting on different cellular targets of major concern in containment, DNA and RNA, and whose expression is under control of different regulatory signals. To engineer the dual gene containment circuit, two toxin-antitoxin pairs, i.e. the colicin E3-immunity E3 and the EcoRI restriction-modification systems, were combined. The genes encoding the immunity E3 and the EcoRI methyltransferase proteins (antitoxins) were stably inserted into the chromosome of the host cell, whereas the broad-host-range lethal genes encoding the colicin E3 RNase and the EcoRI restriction endonuclease (toxins) were flanking the contained trait in a plasmid. This dual lethal cassette decreased gene transfer frequencies, through killing of the recipient cells, by eight orders of magnitude, which provides experimental evidence that the anticipated containment level due to the combination of single containment systems is generally achieved. Survivors that escaped killing were analysed and the mutational events involved were characterized.

Bacterial Proteins↗