{"id":103420,"date":"2018-03-11T10:25:56","date_gmt":"2018-03-11T10:25:56","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/degradacion-endolisosomal-de-p27kip1-mediada-por-snx6-y-papel-de-la-fosforilacion-de-p27kip1-en-el-desarrollo-de-aterosclerosis\/"},"modified":"2018-03-11T10:25:56","modified_gmt":"2018-03-11T10:25:56","slug":"degradacion-endolisosomal-de-p27kip1-mediada-por-snx6-y-papel-de-la-fosforilacion-de-p27kip1-en-el-desarrollo-de-aterosclerosis","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/biologia-celular\/degradacion-endolisosomal-de-p27kip1-mediada-por-snx6-y-papel-de-la-fosforilacion-de-p27kip1-en-el-desarrollo-de-aterosclerosis\/","title":{"rendered":"Degradaci\u00f3n endolisosomal de p27kip1 mediada por snx6 y papel de la fosforilaci\u00f3n de p27kip1 en el desarrollo de aterosclerosis"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Jos\u00e9 Javier Fuster Ortu\u00f1o <\/strong><\/h2>\n<p>La aterosclerosis y los eventos isqu\u00e9micos asociados son la principal causa de morbilidad y mortalidad en los pa\u00edses industrializados. Estudios en humanos y en animales de experimentaci\u00f3n han demostrado que la formaci\u00f3n de la placa ateroscler\u00f3tica es un proceso inflamatorio cr\u00f3nico de origen multifactorial caracterizado por una proliferaci\u00f3n celular excesiva. El inhibidor de ciclo celular p27kip1 es una importante prote\u00edna supresora de tumores que tambi\u00e9n protege frente a la aterosclerosis en el rat\u00f3n. Sin embargo, los mecanismos moleculares que regulan su funci\u00f3n ateroprotectora en la pared arterial permanecen pobremente caracterizados. En la presente tesis doctoral profundizamos en los mecanismos de regulaci\u00f3n de p27kip1, tanto en condiciones fisiol\u00f3gicas como en el contexto patol\u00f3gico de la aterosclerosis. Mediante el empleo de t\u00e9cnicas de inmunofluorescencia, fraccionamiento subcelular y ensayos de p\u00e9rdida y ganancia de funci\u00f3n, hemos demostrado la existencia de una v\u00eda de degradaci\u00f3n endolisosomal de p27kip1 mediada por su interacci\u00f3n con la prote\u00edna snx6. Por otra parte, hemos comprobado que la aterosclerosis humana y murina se asocian con un marcado descenso de la fosforilaci\u00f3n de p27kip1 en la serina 10, y que la deficiencia de esta fosforilaci\u00f3n acelera el desarrollo de aterosclerosis en el rat\u00f3n. Desde un punto de vista mecan\u00edstico, la aterosclerosis exacerbada asociada a la falta de fosforilaci\u00f3n de p27kip1 en la serina 10 no se debe a cambios en la proliferaci\u00f3n celular en la placa ateroscler\u00f3tica, sino a una nueva acci\u00f3n de p27kip1 en el control de la formaci\u00f3n de c\u00e9lulas espumosas mediada por la v\u00eda de se\u00f1alizaci\u00f3n rhoa\/rock. Nuestros resultados desvelan nuevos mecanismos de regulaci\u00f3n y funci\u00f3n de p27kip1 y proporcionan apoyo experimental para el desarrollo de f\u00e1rmacos que induzcan la fosforilaci\u00f3n de p27kip1 en la serina 10 como agentes terap\u00e9uticos de inter\u00e9s para el tratamiento de la aterosclerosis.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Degradaci\u00f3n endolisosomal de p27kip1 mediada por snx6 y papel de la fosforilaci\u00f3n de p27kip1 en el desarrollo de aterosclerosis<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Degradaci\u00f3n endolisosomal de p27kip1 mediada por snx6 y papel de la fosforilaci\u00f3n de p27kip1 en el desarrollo de aterosclerosis <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Jos\u00e9 Javier Fuster Ortu\u00f1o <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Universitat de val\u00e9ncia (estudi general)<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 29\/07\/2010<\/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>Vicente Andr\u00e9s Garc\u00eda<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: vicente Rubio zamora <\/li>\n<li>Mar\u00eda Jes\u00fas Sanz ferrando (vocal)<\/li>\n<li>lisardo Bosc\u00e1 gomar (vocal)<\/li>\n<li>Francisco Sanchez Madrid (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Jos\u00e9 Javier Fuster Ortu\u00f1o La aterosclerosis y los eventos isqu\u00e9micos asociados son la principal causa de morbilidad [&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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