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M Rallu

Publications and source records attributed to M Rallu.

8 recordsLinked to original sources
PubMed2001

Gene trap insertion reveals two open reading frames in the mouse SSeCKS gene: the form predominantly detected in the nervous system is suppressed by the insertion while the other, specific of the testis, remains expressed.

Scaffold proteins play an important role in regulating signal transduction by targeting kinases and phosphatases in close proximity to their relevant substrates. SSeCKS protein has been described as a protein kinase C and A (PKC/PKA) anchoring protein as well as a PKC substrate with a tumor suppressor activity. In this study, we report the generation, via gene trapping in embryonic stem cells of mice carrying an insertion in the mouse SSeCKS gene. Through the molecular analysis of the insertion site, we show that SSeCKS contains two alternative promoters directing the synthesis of mRNAs (P1- and P2-mRNA), encoding two different proteins, one of which would be a truncated form of the other. Interestingly, these RNAs are differentially expressed, P2 being found exclusively in the male germ line, while P1 exhibits a dynamic and wider pattern of expression during embryonic development and in the adult; its expression is predominant in the nervous system. Finally, we show that P1- but not P2-mRNA expression is abolished by the insertion and furthermore that mice homozygous for the mutation lack SSeCKS in all tissues except the male germ cells. Nevertheless and surprisingly, these mice do not exhibit any obvious phenotype. The functional implications of these observations are discussed.

A Kinase Anchor Proteins↗
PubMed2000

Cyclosporin A induces an atypical heat shock response.

Cyclosporin A is a widely used immunosuppressive drug having toxic side effects, in particular on kidneys and liver, as a result of its action on different molecular targets. Here we demonstrate that low doses of CsA are able to induce the expression of the heat shock protein HSP27 and its hyperphosphorylation. It also activates the two heat shock transcription factors, HSF1 and HSF2. Since these factors have been shown to be activated by proteasome inhibition, we tested the hypothesis that the inhibitory action of CsA on the proteasome might be responsible for the activation of HSFs and the subsequent expression of HSP27. The increase in multiubiquitinated proteins as well as the stabilization of p53 following CsA addition argues in favor of this hypothesis. The kidney BSC-1 cells are highly responsive to the addition of CsA: the possible link between HSP27 induction and hyperphosphorylation and nephrotoxicity is discussed.

Animals↗
PubMed1997

Function and regulation of heat shock factor 2 during mouse embryogenesis.

The spontaneous expression of heat shock genes during development is well documented in many animal species, but the mechanisms responsible for this developmental regulation are only poorly understood. In vertebrates, additional heat shock transcription factors, distinct from the heat shock factor 1 (HSF1) involved in the stress response, were suggested to be involved in this developmental control. In particular, the mouse HSF2 has been found to be active in testis and during preimplantation development. However, the role of HSF2 and its mechanism of activation have remained elusive due to the paucity of data on its expression during development. In this study, we have examined HSF2 expression during the postimplantation phase of mouse development. Our data show a developmental regulation of HSF2, which is expressed at least until 15.5 days of embryogenesis. It becomes restricted to the central nervous system during the second half of gestation. It is expressed in the ventricular layer of the neural tube which contains mitotically active cells but not in postmitotic neurons. Parallel results were obtained for mRNA, protein, and activity levels, demonstrating that the main level of control was transcriptional. The detailed analysis of the activity of a luciferase reporter gene under the control of the hsp70.1 promoter, as well as the description of the protein expression patterns of the major heat shock proteins in the central nervous system, show that HSF2 and heat shock protein expression domains do not coincide. This result suggests that HFS2 might be involved in other regulatory developmental pathways and paves the way to new functional approaches.

Animals↗
PubMed1997

HSP gene expression and HSF2 in mouse development.

During the pre-implantation phase of development, the mouse embryo synthesizes HSC70, and HSP90 alpha and beta at a very high rate. After implantation, the expression of HSPs appears non-coordinated and is not uniform in the different tissues. The expression of inducible HSPs appears later in development than that of constitutive members of the family. HSP25 is highly expressed early in heart and muscle development, but also in some structure of the central nervous system. HSC70 and HSP90 beta are expressed ubiquitously, but their expression reaches very high levels in the nervous system (neural tracks) and during bone morphogenesis (in the hypertrophic chondrocytes). The mechanisms involved in HSP expression during mouse embryogenesis are probably diverse, involving tissue-specific sequences. Although the DNA-binding activity and expression of the second heat shock transcription factor, HSF2, seems to be developmentally regulated, becoming detectable at the blastocyst stage and reaching a peak at day 10 of development, there is no obvious correlation between the level of this factor and the expression of HSPs. HSF2 might be involved in the onset of expression of HSPs, regulate (inhibit) their expression, or control the expression of other developmental genes yet to be discovered.

Animals↗
PubMed1997

Evidence for the involvement of mouse heat shock factor 1 in the atypical expression of the HSP70.1 heat shock gene during mouse zygotic genome activation.

The mouse HSP70.1 gene, which codes for a heat shock protein (hsp70), is highly transcribed at the onset of zygotic genome activation (ZGA). This expression, which occurs in the absence of stress, is then repressed. It has been claimed that this gene does not exhibit a stress response until the blastocyst stage. The promoter of HSP70.1 contains four heat shock element (HSE) boxes which are the binding sites of heat shock transcription factors (HSF). We have been studying the presence and localization of the mouse HSFs, mHSF1 and mHSF2, at different stages of embryo development. We show that mHSF1 is already present at the one-cell stage and concentrated in the nucleus. Moreover, by mutagenizing HSE sequences and performing competition experiments (in transgenic embryos with the HSP70.1 promoter inserted before a reporter gene), we show that, in contrast with previous findings, HSE boxes are involved in this spontaneous activation. Therefore, we suggest that HSF1 and HSE are important in this transient expression at the two-cell stage and that the absence of typical inducibility at this early stage of development results mainly from the high level of spontaneous transcription of this gene during the ZGA.

Animals↗
PubMed1994

Heat shock factor 2-like activity in mouse blastocysts.

The expression of heat shock genes is induced in all living cells by a series of proteotoxic treatments. Heat shock genes are also activated spontaneously during different phases of embryonic development. HSP89 alpha and HSC70 are expressed at a high level in the mouse blastocyst. A family of factors, called HSFs, are able to bind to the promoters of heat shock genes on upstream conserved elements (HSEs). HSF1 is unable to bind to HSE sequences in absence of stress. It is activated after a stress by post-translational modifications and conformational change. HSF2 shows common structural domains with HSF1; however, it is active at normal temperatures. Recently we showed the presence of an abundant HSE-binding activity in nonshocked blastocysts. We demonstrate here by using polyclonal antibodies that HSF2 is the major constituent of this constitutive HSE-binding activity. HSF2 might be involved in the control of heat shock gene expression during early mammalian embryogenesis.

Animals↗
PubMed1992

Mammalian heat shock protein families. Expression and functions.

When prokaryotic or eukaryotic cells are submitted to a transient rise in temperature or to other proteotoxic treatments, the synthesis of a set of proteins called the heat shock proteins (hsp) is induced. The structure of these proteins has been highly conserved during evolution. The signal leading to the transcriptional activation of the corresponding genes is the accumulation of denatured and/or aggregated proteins inside the cells after stressful treatment. The expression of a subset of hsp is also induced during early embryogenesis and many differentiation processes. Two different functions have been ascribed to hsp: a molecular chaperone function: chaperones mediate the folding, assembly or translocation across the intracellular membranes of other polypeptides, and a role in protein degradation: some of the essential components of the cytoplasmic ubiquitin-dependent degradative pathway are hsp. These functions of hsp are essential in every living cell. They are required for repairing the damage resulting from stress.

Animals↗