{"id":105095,"date":"2018-03-11T10:28:27","date_gmt":"2018-03-11T10:28:27","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/regulatory-mechanisms-of-c-myc-and-their-role-in-acute-myeloid-leukemia\/"},"modified":"2018-03-11T10:28:27","modified_gmt":"2018-03-11T10:28:27","slug":"regulatory-mechanisms-of-c-myc-and-their-role-in-acute-myeloid-leukemia","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/biologia-humana\/regulatory-mechanisms-of-c-myc-and-their-role-in-acute-myeloid-leukemia\/","title":{"rendered":"Regulatory mechanisms of c-myc and their role in acute myeloid leukemia"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Iris Uribesalgo Mic\u00c1\u00a0s <\/strong><\/h2>\n<p>El factor de transcripci\u00f3n c-myc juega un papel clave en la homeostasis celular, encontr\u00e1ndose frecuentemente desregulado en la carcinog\u00e9nesis humana. C-myc promueve la progresi\u00f3n de ciclo celular mediante la activaci\u00f3n o represi\u00f3n de genes diana formando un complejo con la prote\u00edna max. La sobre-expresi\u00f3n de c-myc tambi\u00e9n inhibe la diferenciaci\u00f3n celular, aunque los mecanismos exactos de dicha represi\u00f3n son desconocidos. La heterodimerizaci\u00f3n con max se considera estrictamente necesaria para todas las actividades transcripcionales y oncog\u00e9nicas de c-myc, de manera que el desarrollo de inhibidores de la dimerizaci\u00f3n de c-myc con max se ambiciona como terapia antitumoral. Sin embargo, diversas observaciones sugieren que c-myc tienen funciones independientes de max, aunque no han sido totalmente caracterizadas.  en esta tesis se ha estudiado de qu\u00e9 manera diferentes mecanismos reguladores pueden frenar la actividad oncog\u00e9nica de c-myc y el subsiguiente impacto en la diferenciaci\u00f3n celular. En la primera mitad de la tesis, se demuestra que pml promueve la desestabilizaci\u00f3n de la prote\u00edna c-myc y, en consecuencia, la reactivaci\u00f3n de los genes diana reprimidos por c-myc. Entre estos genes diana se encuentra el inhibidor del ciclo celular cdkn1\/p21, la reexpresi\u00f3n del cual provoca la diferenciaci\u00f3n de c\u00e9lulas leuc\u00e9micas inducida por pml. En la segunda mitad, se identifica un nuevo mecanismo de regulaci\u00f3n transcripcional por parte de c-myc a trav\u00e9s de la interacci\u00f3n con rara, el cual est\u00e1 unido al adn. En c\u00e9lulas indiferenciadas, los d\u00edmeros c-myc\/max cooperan con rara en la represi\u00f3n de genes esenciales para la diferenciaci\u00f3n. Una vez c-myc es fosforilado por la quinasa pak2, el complejo de c-myc con rara se convierte en activador mediante la p\u00e9rdida de max y el reclutamiento de coactivadores transcripcionales. Este descubrimiento supone un nuevo mecanismo mediante el cual c-myc puede ejercer la regulaci\u00f3n g\u00e9nica al menos en parte independientemente de max, y tambi\u00e9n revela una funci\u00f3n desconocida de c-myc en la inhibici\u00f3n y la promoci\u00f3n de la diferenciaci\u00f3n celular.  en conjunto, estos resultados describen dos nuevos mecanismos que contrarrestan la actividad oncog\u00e9nica de c-myc. Pml y pak2 pueden ser considerados supresores de tumores ya que modulan la funci\u00f3n de c-myc para promover la diferenciaci\u00f3n de las c\u00e9lulas leuc\u00e9micas. Estos descubrimientos pueden utilizarse como base para el desarrollo de nuevas terapias antitumorales que tengan como diana la prote\u00edna c-myc.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Regulatory mechanisms of c-myc and their role in acute myeloid leukemia<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Regulatory mechanisms of c-myc and their role in acute myeloid leukemia <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Iris Uribesalgo Mic\u00c1\u00a0s <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Pompeu fabra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 24\/11\/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>Luciano Di Croce<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: purificacion Mu\u00f1oz canoves <\/li>\n<li>susana De la luna gargantilla (vocal)<\/li>\n<li>  (vocal)<\/li>\n<li>  (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Iris Uribesalgo Mic\u00c1\u00a0s El factor de transcripci\u00f3n c-myc juega un papel clave en la homeostasis celular, encontr\u00e1ndose [&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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