49 research outputs found

    PPM1D (protein phosphatase 1D magnesium-dependent, delta isoform)

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    Review on PPM1D (protein phosphatase 1D magnesium-dependent, delta isoform), with data on DNA, on the protein encoded, and where the gene is implicated

    Parable in Nikolai Gogolā€™s works: specifics of the author's presentation

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    The parable of the works of N.V. Gogol as one of the most important elements of the writer's strategy is analyzed. Emphasis is placed both on its formal and content embodiment in the author's works. The formal part shows the important connection between the parable and the artistic detail of the literary work and the composition on the whole. The content part deals with the writer, who builds a complex system of conflicts and their role in the plot scheme. For the study, researchers consider it necessary to warn against a shallow analysis of Gogol's parable as a kind of vulgar form of reasonableness or teaching. Reading the author's texts shows that the parable departs from the classical model and resembles ā€œdie Parabelā€, a form of parable in the literature of European modernism, which complicates and makes the edifying aspect less obvious. The parable element considered in this work should be studied not in general terms, but as an integral part of the poetics and artistic system of the author, which allows us to consider this phenomenon in more detail, as an individually mastered part of the composition of the work of a single author. Using this approach, it is possible to show Gogol as a phenomenon of world literature, and the reason for that is a complex system of parables, implemented in different ways in his literary works. This system absorbs particular elements of poetics using a variety of functions that form a single system of artistic originality of Gogol's texts. Moreover, it emphasizes the originality of texts and their dissimilarity from each other even within the author's collection

    Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites

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    PPM1D (Wip1), a type PP2C phosphatase, is expressed at low levels in most normal tissues but is overexpressed in several types of cancers. In cells containing wild-type p53, the levels of PPM1D mRNA and protein increase following exposure to genotoxic stress, but the mechanism of regulation by p53 was unknown. PPM1D also has been identified as a CREB-regulated gene due to the presence of a cyclic AMP response element (CRE) in the promoter. Transient transfection and chromatin immunoprecipitation experiments in HCT116 cells were used to characterize a conserved p53 response element located in the 5ā€² untranslated region (UTR) of the PPM1D gene that is required for the p53-dependent induction of transcription from the human PPM1D promoter. CREB binding to the CRE contributes to the regulation of basal expression of PPM1D and directs transcription initiation at upstream sites. Following exposure to ultraviolet (UV) or ionizing radiation, the abundance of transcripts with short 5ā€² UTRs increased in cells containing wild-type p53, indicating increased utilization of downstream transcription initiation sites. In cells containing wild-type p53, exposure to UV resulted in increased PPM1D protein levels even when PPM1D mRNA levels remained constant, indicating post-transcriptional regulation of PPM1D protein levels

    Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites

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    PPM1D (Wip1), a type PP2C phosphatase, is expressed at low levels in most normal tissues but is overexpressed in several types of cancers. In cells containing wild-type p53, the levels of PPM1D mRNA and protein increase following exposure to genotoxic stress, but the mechanism of regulation by p53 was unknown. PPM1D also has been identified as a CREB-regulated gene due to the presence of a cyclic AMP response element (CRE) in the promoter. Transient transfection and chromatin immunoprecipitation experiments in HCT116 cells were used to characterize a conserved p53 response element located in the 5ā€² untranslated region (UTR) of the PPM1D gene that is required for the p53-dependent induction of transcription from the human PPM1D promoter. CREB binding to the CRE contributes to the regulation of basal expression of PPM1D and directs transcription initiation at upstream sites. Following exposure to ultraviolet (UV) or ionizing radiation, the abundance of transcripts with short 5ā€² UTRs increased in cells containing wild-type p53, indicating increased utilization of downstream transcription initiation sites. In cells containing wild-type p53, exposure to UV resulted in increased PPM1D protein levels even when PPM1D mRNA levels remained constant, indicating post-transcriptional regulation of PPM1D protein levels

    Clonal haematopoiesis - a novel entity that modifies pathological processes in elderly

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    Abstract Progress in the development of new sequencing techniques with wider accessibility and higher sensitivity of the protocol of deciphering genome particularities led to the discovery of a new phenomenon ā€“ clonal haematopoiesis. It is characterized by the presence in the bloodstream of elderly people a minor clonal population of cells with mutations in certain genes, but without any sign of disease related to the hematopoietic system. Here we will review this recent advancement in the field of clonal haematopoiesis and how it may affect the diseaseā€™s development in old age

    Wip1 phosphatase: between p53 and MAPK kinases pathways

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    IF 5.008International audienceCells undergoing oncogenic transformation frequently inactivate tumor suppressor pathways that could prevent their uncontrolled growth. Among those pathways p53 and p38MAPK pathways play a critical role in regulation of cell cycle, senescence and cell death in response to activation of oncogenes, stress and DNA damage. Consequently, these two pathways are important in determining the sensitivity of tumor cells to anti-cancer treatment. Wild type p53-induced phosphatase, Wip1, is involved in governance of both pathways. Recently, strategies directed to manipulation with Wip1 activity proposed to advance current day anticancer treatment and novel chemical compounds synthesized to improve specificity of manipulation with Wip1 activity. Here we reviewed the history of Wip1 studies in vitro and in vivo, in genetically modified animal models that support Wip1 role in tumorigenesis through regulation of p53 and p38MAPK pathways. Based on our knowledge we propose several recommendations for future more accurate studies of Wip1 interactions with other pathways involved in tumorigenesis using recently developed tools and for adoption of Wip1 manipulation strategies in anti-cancer therapy

    Induction of PPM1D following DNA-damaging

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    treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation site

    Wip1 inhibition leads to severe pro-inflammatory phenotype in skin in response to chemical irritation

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    IF 3.733Lettre Ć  l'Ć©diteur ("Journal of Dermatological Science" vol. 87, nĀ°1)http://www.sciencedirect.com/science/article/pii/S0923181116309252?via%3Dihu
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