3 resultados para Cis-acting regulatory variants
em Repositório Científico do Instituto Politécnico de Lisboa - Portugal
Resumo:
The general transcription factor TFIIB, encoded by SUA7 in Saccharomyces cerevisiae, is required for transcription activation but apparently of a specific subset of genes, for example, linked with mitochondrial activity and hence with oxidative environments. Therefore, studying SUA7/TFIIB as a potential target of oxidative stress is fundamental. We found that controlled SUA7 expression under oxidative conditions occurs at transcriptional and mRNA stability levels. Both regulatory events are associated with the transcription activator Yap1 in distinct ways: Yap1 affects SUA7 transcription up regulation in exponentially growing cells facing oxidative signals; the absence of this activator per se contributes to increase SUA7 mRNA stability. However, unlike SUA7 mRNA, TFIIB abundance is not altered on oxidative signals. The biological impact of this preferential regulation of SUA7 mRNA pool is revealed by the partial suppression of cellular oxidative sensitivity by SUA7 overexpression, and supported by the insights on the existence of a novel RNA-binding factor, acting as an oxidative sensor, which regulates mRNA stability. Taken together the results point out a primarily cellular commitment to guarantee SUA7 mRNA levels under oxidative environments.
Resumo:
Background: CDC25 phosphatases control cell cycle progression by activating cyclin dependent kinases. The three CDC25 isoforms encoding genes are submitted to alternative splicing events which generate at least two variants for CDC25A and five for both CDC25B and CDC25C. An over-expression of CDC25 was reported in several types of cancer, including breast cancer, and is often associated with a poor prognosis. Nevertheless, most of the previous studies did not address the expression of CDC25 splice variants. Here, we evaluated CDC25 spliced transcripts expression in anti-cancerous drug-sensitive and resistant breast cancer cell lines in order to identify potential breast cancer biomarkers. Methods: CDC25 splice variants mRNA levels were evaluated by semi-quantitative RT-PCR and by an original real-time RT-PCR assay. Results: CDC25 spliced transcripts are differentially expres-sed in the breast cancer cell lines studied. An up-regulation of CDC25A2 variant and an increase of the CDC25C5/C1 ratio are associated to the multidrug-resistance in VCREMS and DOXOR breast cancer cells, compared to their sensitive counterpart cell line MCF-7. Additionally, CDC25B2 tran-script is exclusively over-expressed in VCREMS resistant cells and could therefore be involved in the development of certain type of drug resistance. Conclusions: CDC25 splice variants could represent interesting potential breast cancer prognostic biomarkers.
Resumo:
In the last years the electricity industry has faced a restructuring process. Among the aims of this process was the increase in competition, especially in the generation activity where firms would have an incentive to become more efficient. However, the competitive behavior of generating firms might jeopardize the expected benefits of the electricity industry liberalization. The present paper proposes a conjectural variations model to study the competitive behavior of generating firms acting in liberalized electricity markets. The model computes a parameter that represents the degree of competition of each generating firm in each trading period. In this regard, the proposed model provides a powerful methodology for regulatory and competition authorities to monitor the competitive behavior of generating firms. As an application of the model, a study of the day-ahead Iberian electricity market (MIBEL) was conducted to analyze the impact of the integration of the Portuguese and Spanish electricity markets on the behavior of generating firms taking into account the hourly results of the months of June and July of 2007. The advantages of the proposed methodology over other methodologies used to address market power, namely Residual Supply index and Lerner index are highlighted. (C) 2014 Elsevier Ltd. All rights reserved.