{"id":67860,"date":"2008-07-11T00:00:00","date_gmt":"2008-07-11T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/role-of-the-transcription-factor-nfat5-in-mammalian-cell-cycle-regulation\/"},"modified":"2008-07-11T00:00:00","modified_gmt":"2008-07-11T00:00:00","slug":"role-of-the-transcription-factor-nfat5-in-mammalian-cell-cycle-regulation","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/biologia-celular\/role-of-the-transcription-factor-nfat5-in-mammalian-cell-cycle-regulation\/","title":{"rendered":"Role of the transcription factor nfat5 in mammalian cell cycle regulation"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Katherine Drews Elger <\/strong><\/h2>\n<p>El factor de transcripci\u00f3n nfat5 (nuclear factor of activated t cells 5)\/tonebp pertenece a la familia rel, a la cual adem\u00e1s pertenecen las prote\u00ednas nf-kb y nfatc. El nfat5 muestra homolog\u00eda estructural y funcional con los dem\u00e1s miembros de la familia rel \u00fanicamente a nivel del dominio de uni\u00f3n al adn, diferenci\u00e1ndose considerablemente en las dem\u00e1s regiones. El nfat5 permite a las c\u00e9lulas adaptarse y tolerar ambientes hipert\u00f3nicos por medio de la regulaci\u00f3n de un programa osmoprotector de expresi\u00f3n g\u00e9nica, cuyos productos incluyen chaperonas as\u00ed como transportadores y enzimas que aumentan la concentraci\u00f3n de osmolitos org\u00e1nicos. La supresi\u00f3n del nfat5 en rat\u00f3n causa alta mortalidad embri\u00f3nica y perinatal, y los animales supervivientes muestran retraso en el crecimiento, as\u00ed como atrofia renal y disfunci\u00f3n linfocitaria asociada a una inadecuada respuesta a la hipertonicidad.   ya que existe una alta mortalidad en los ratones deficientes para el nfat5, generamos ratones en los cuales la supresi\u00f3n de este factor se realiza de manera espec\u00edfica en un tipo celular. En este trabajo hemos investigado la respuesta a estr\u00e9s osm\u00f3tico en linfocitos t que carecen del nfat5. Las c\u00e9lulas t proliferantes expuestas a estr\u00e9s hiperosm\u00f3tico responden de manera bif\u00e1sica, con una fase temprana, en gran parte independiente del nfat5, seguida de una fase de adaptaci\u00f3n dependiente del nfat5. En la fase temprana se observ\u00f3 un patr\u00f3n con caracter\u00edsticas similares a la respuesta al estr\u00e9s genot\u00f3xico, que inclu\u00eda la inducci\u00f3n de los marcadores de estr\u00e9s p53, p21 y gadd45, as\u00ed como la disminuci\u00f3n de los niveles de ciclinas y aurora quinasa b. La fase de adaptaci\u00f3n, mediada por el nfat5, incluye la disminuci\u00f3n de los niveles de marcadores de estr\u00e9s, la inducci\u00f3n de genes osmoprotectores, as\u00ed como la reanudaci\u00f3n de la expresi\u00f3n de ciclinas y progresi\u00f3n del ciclo celular. En esta fase, las c\u00e9lulas deficientes para el nfat5, presentan defectos en la inducci\u00f3n de genes osmoprotectores y adem\u00e1s de un arresto del ciclo celular debido a bajos niveles de ciclinas en las fases s y g2\/m.   finalmente, la activaci\u00f3n de linfocitos t que carecen del nfat5 y son expuestas a niveles de estr\u00e9s hipert\u00f3nico equivalentes a aquellos registrados en pacientes con desequilibrio electrol\u00edtico y en modelos de animales deficientes en mol\u00e9culas osmoreguladoras, causa la inhibici\u00f3n de la expresi\u00f3n de ciclinas, aurora quinasa b, as\u00ed como de la progresi\u00f3n del ciclo celular. Nuestros resultados apoyan la conclusi\u00f3n que la activaci\u00f3n de un programa osmoprotector de expresi\u00f3n g\u00e9nica, dirigido por el nfat5, permite la proliferaci\u00f3n celular bajo condiciones de estr\u00e9s hiperosm\u00f3tico, ya que su presencia es necesaria para la expresi\u00f3n de ciclinas principalmente de las fases s y g2\/m, y la aurora b quinasa.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Role of the transcription factor nfat5 in mammalian cell cycle regulation<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Role of the transcription factor nfat5 in mammalian cell cycle regulation <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Katherine Drews Elger <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Pompeu fabra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 07\/11\/2008<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Jos\u00e9 Francisco Aramburu Beltran<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Francisco xavier Real arribas <\/li>\n<li>joan Albanell mestres (vocal)<\/li>\n<li>purificacion Mu\u00f1oz canoves (vocal)<\/li>\n<li>anna Bigas salvans (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Katherine Drews Elger El factor de transcripci\u00f3n nfat5 (nuclear factor of activated t cells 5)\/tonebp pertenece a [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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