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Abstract:

Bcl-X exists in at least five different isoforms with complex effects on programmed cell death. Glucocorticoids and progestins control bcl-X expression and influence the ratio between bcl-XL (antiapoptotic isoform) and bcl-XS (proapoptotic isoform) in different tissues. The 5′-UTR region of the mouse bcl-X gene contains at least five different promoters, which exhibit a tissue-specific pattern of promoter usage. Several mRNAs with different 5′-leading exons can be generated upon promoter activation. Here we explore the potential of the various bcl-X gene promoters to be regulated by glucocorticoids or progestins. We found that the region located immediately upstream of promoter 4 (P4) contains two hormone response element (HRE)-like sequences at positions -3040 (HRE I) and -3001 (HRE II) relative to the translation initiation codon. These HRE-like sequences confer hormone responsiveness to a core promoter and bind glucocorticoid or progesterone receptors in vitro. Point mutations of both HREs that prevent steroid receptor binding also eliminate hormonal inducibility. In cells treated with glucocorticoids, the hormone receptor is recruited to the P4 region containing the HREs. Analysis of the products of the endogenous bcl-X in epithelial mammary cells showed that only transcripts originating from P4 increased upon hormone treatment. This observation correlates with the induction of the bcl-XL mRNA, suggesting that P4 is one of the bcl-X promoters responsible for the generation of this antiapoptotic isoform.

Registro:

Documento: Artículo
Título:Steroid Hormones Induce bcl-X Gene Expression through Direct Activation of Distal Promoter P4
Autor:Viegas, L.R.; Vicent, G.P.; Barañao, J.L.; Beato, M.; Pecci, A.
Filiación:Depto. de Quimica Biologica, Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Ctr. de Regulacio Genomica, Barcelona, Spain
Centre de Regulacio Genomica, Passeig Maritim 37-49, E-08003 Barcelona, Spain
Palabras clave:Chemical bonds; Correlation methods; Cytology; Genes; RNA; Tissue; Epithelial cells; Mutants; Hormones; gestagen; glucocorticoid; protein bcl x; steroid hormone; alternative RNA splicing; animal cell; article; cell death; cell type; codon; controlled study; enhancer region; epithelium cell; gene activation; gene expression regulation; gene induction; hormone response; hormone responsive element; nonhuman; point mutation; priority journal; promoter region; protein family; protein protein interaction; tissue specificity; translation initiation; Animals; Apoptosis; Base Sequence; bcl-X Protein; Binding, Competitive; Cell Line; Cell Nucleus; Chromatin; Codon; COS Cells; DNA; Exons; Gene Expression Regulation; Genetic Vectors; Glucocorticoids; Mice; Models, Genetic; Molecular Sequence Data; Open Reading Frames; Plasmids; Point Mutation; Precipitin Tests; Progestins; Promoter Regions (Genetics); Protein Binding; Protein Biosynthesis; Protein Isoforms; Proto-Oncogene Proteins c-bcl-2; Receptors, Progesterone; Recombinant Proteins; RNA; RNA, Messenger; Steroids; Sulfuric Acid Esters; Transfection; Animalia
Año:2004
Volumen:279
Número:11
Página de inicio:9831
Página de fin:9839
DOI: http://dx.doi.org/10.1074/jbc.M312402200
Título revista:Journal of Biological Chemistry
Título revista abreviado:J. Biol. Chem.
ISSN:00219258
CODEN:JBCHA
CAS:bcl-X Protein; Bcl2l1 protein, mouse; Chromatin; Codon; dimethyl sulfate, 77-78-1; DNA, 9007-49-2; Glucocorticoids; Progestins; Protein Isoforms; Proto-Oncogene Proteins c-bcl-2; Receptors, Progesterone; Recombinant Proteins; RNA, 63231-63-0; RNA, Messenger; Steroids; Sulfuric Acid Esters
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v279_n11_p9831_Viegas

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Citas:

---------- APA ----------
Viegas, L.R., Vicent, G.P., Barañao, J.L., Beato, M. & Pecci, A. (2004) . Steroid Hormones Induce bcl-X Gene Expression through Direct Activation of Distal Promoter P4. Journal of Biological Chemistry, 279(11), 9831-9839.
http://dx.doi.org/10.1074/jbc.M312402200
---------- CHICAGO ----------
Viegas, L.R., Vicent, G.P., Barañao, J.L., Beato, M., Pecci, A. "Steroid Hormones Induce bcl-X Gene Expression through Direct Activation of Distal Promoter P4" . Journal of Biological Chemistry 279, no. 11 (2004) : 9831-9839.
http://dx.doi.org/10.1074/jbc.M312402200
---------- MLA ----------
Viegas, L.R., Vicent, G.P., Barañao, J.L., Beato, M., Pecci, A. "Steroid Hormones Induce bcl-X Gene Expression through Direct Activation of Distal Promoter P4" . Journal of Biological Chemistry, vol. 279, no. 11, 2004, pp. 9831-9839.
http://dx.doi.org/10.1074/jbc.M312402200
---------- VANCOUVER ----------
Viegas, L.R., Vicent, G.P., Barañao, J.L., Beato, M., Pecci, A. Steroid Hormones Induce bcl-X Gene Expression through Direct Activation of Distal Promoter P4. J. Biol. Chem. 2004;279(11):9831-9839.
http://dx.doi.org/10.1074/jbc.M312402200