{"id":64856,"date":"2018-03-09T22:52:55","date_gmt":"2018-03-09T22:52:55","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/caracterizacion-funcional-de-la-molecula-proapoptotica-bak-en-el-reta%c2%adculo-endoplasmatico\/"},"modified":"2018-03-09T22:52:55","modified_gmt":"2018-03-09T22:52:55","slug":"caracterizacion-funcional-de-la-molecula-proapoptotica-bak-en-el-reta%c2%adculo-endoplasmatico","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/salamanca\/caracterizacion-funcional-de-la-molecula-proapoptotica-bak-en-el-reta%c2%adculo-endoplasmatico\/","title":{"rendered":"Caracterizaci\u00f3n funcional de la mol\u00e9cula proapopt\u00f3tica bak en el ret\u00edculo endoplasm\u00e1tico"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Martina Klee <\/strong><\/h2>\n<p>Bak y bax son miembros proapopt\u00f3ticos de la familia bcl-2 que presentan una alta redundancia funcional. Ambos hom\u00f3logos constituyen un punto de control cr\u00edtico en la v\u00eda mitocondrial de apoptosis y est\u00e1n localizados tanto en la mitocondria como en el ret\u00edculo endoplasm\u00e1tico (re). Mientras que ya se ha establecido que bak y bax mitocondriales son suficientes para la inducci\u00f3n de apoptosis por prote\u00ednas bh3-only, todav\u00eda se desconoce en gran medida el papel de los hom\u00f3logos reticulares, aunque parecen controlar la apoptosis a trav\u00e9s de la regulaci\u00f3n de los niveles de calcio. mediante diferentes ensayos de sobreexpresi\u00f3n hemos determinado dos nuevas actividades de bak reticular. Por un lado, bak tiene la capacidad de modular la estructura del re. La coexpresi\u00f3n de bak con bclxl provoca la vacuolizaci\u00f3n y dilataci\u00f3n acusada de las cisternas reticulares. Un mutante de bak carente del dominio bh3 es suficiente para inducir este fenotipo, y una versi\u00f3n reticular de bakdeltabh3 retiene esta actividad. La expresi\u00f3n de activadores como bim o tbid en condiciones similares recapitula la dilataci\u00f3n reticular y la vacuolizaci\u00f3n cuando los receptores de calcio de tipo rianodina est\u00e1n inhibidos. Experimentos con c\u00e9lulas fibrobl\u00e1sticas embrionarias murinas (mef) deficientes en bak y bax muestran que bak end\u00f3geno media este efecto, mientras que bax es mayoritariamente irrelevante. Estos resultados, por tanto, constituyen un ejemplo de divergencia funcional entre los dos hom\u00f3logos multidominio. Por otro lado, hemos demostrado que c\u00e9lulas mef que expresan exclusivamente bak reticular en ausencia de bax end\u00f3geno movilizan citocromo c e inducen apoptosis en respuesta a los efectores bimel y puma. De forma sorprendente, calcio es necesario pero no suficiente para mediar la v\u00eda de se\u00f1alizaci\u00f3n, a pesar de niveles normales de calcio reticular. Nuestros resultados indican que el calcio funciona en coordinaci\u00f3n con la maquinaria celular a situaciones del estr\u00e9s reticular ire1\u00c2\u00bf\/traf2 para transmitir se\u00f1ales apopt\u00f3ticas desde el re a la mitocondria. Estos datos revelan que mol\u00e9culas bh3-only requieren bak reticular para activar una v\u00eda de se\u00f1alizaci\u00f3n re-mitocondria capaz de inducir la movilizaci\u00f3n del citocromo c y apoptosis de forma independiente de la maquinar\u00eda mitocondrial can\u00f3nica dependiente de bak y bax en este org\u00e1nulo, lo que a\u00f1ade un nuevo nivel de complejidad a la regulaci\u00f3n apopt\u00f3tica.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Caracterizaci\u00f3n funcional de la mol\u00e9cula proapopt\u00f3tica bak en el ret\u00edculo endoplasm\u00e1tico<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Caracterizaci\u00f3n funcional de la mol\u00e9cula proapopt\u00f3tica bak en el ret\u00edculo endoplasm\u00e1tico <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Martina Klee <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Salamanca<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 30\/05\/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>Felipe Pimentel Mui\u00f1os<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: abelardo L\u00f3pez rivas <\/li>\n<li>faustino Mollinedo Garc\u00eda (vocal)<\/li>\n<li>Juan  pedro Bola\u00f1os hernandez (vocal)<\/li>\n<li>Jos\u00e9 Alberto Garc\u00eda sanz (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Martina Klee Bak y bax son miembros proapopt\u00f3ticos de la familia bcl-2 que presentan una alta redundancia [&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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