{"id":115297,"date":"2018-03-11T10:43:42","date_gmt":"2018-03-11T10:43:42","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/caracterizacion-estructural-del-supresor-tumoral-ing5\/"},"modified":"2018-03-11T10:43:42","modified_gmt":"2018-03-11T10:43:42","slug":"caracterizacion-estructural-del-supresor-tumoral-ing5","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/proteinas\/caracterizacion-estructural-del-supresor-tumoral-ing5\/","title":{"rendered":"Caracterizaci\u00f3n estructural del supresor tumoral ing5"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Jhon Alexander Rodriguez Buitrago <\/strong><\/h2>\n<p>Los genes de la familia de ing (inhibitors of growth) se clasifican como supresores de tumores en base a estudios donde  se muestra la existencia de p\u00e9rdida, desregulaci\u00f3n y disminuci\u00f3n de  expresi\u00f3n en diferentes tipos de c\u00e1ncer (piche &#038;  li, 2010). En varios estudios se ha propuesto que todos los miembros de la familia ing cooperan con p53 para inducir apoptosis y senescencia (cheung &#038; li, 2002; jafarnejad &#038; li; nagashima et al, 2003; shiseki  et al, 2003). En esta tesis se realiz\u00f3 un estudio estructural de la prote\u00edna ing5 humana. Los resultados obtenidos permiten concluir que ing5 un d\u00edmero asim\u00e9trico constituido por tres dominios estructuralmente independientes: un dominio n-terminal plegado que al igual que el homologo ing4 es la regi\u00f3n de dimerizaci\u00f3n, un dominio central desestructurado y flexible, y un dominio c-terminal plegado de tipo phd a trav\u00e9s el cual interacciona con la histona h3 del nucleosoma. La estructura del dominio n-terminal de ing5 observada en disoluci\u00f3n por rmn es sim\u00e9trica. Las interacciones observadas en la estructura cristalina y la conservaci\u00f3n de los residuos  implicados sugieren que las estructuras sim\u00e9trica y asim\u00e9trica podr\u00edan estar reguladas por el equilibrio de prot\u00f3naci\u00f3n de residuos de histidina (h9 y h96). El an\u00e1lisis de los mutantes puntuales en el dominio n-terminal de ing5 detectados en c\u00e1ncer q33r, i68v y c75r indica que son menos estables que la prote\u00edna nativa. Especialmente inestable es el mutante c75r, con una temperatura media aparente de desnaturalizaci\u00f3n por debajo de la fisiol\u00f3gica. Ing5 se une a la prote\u00edna al dominio iib de la prote\u00edna jade, pero no se conoce el sitio de interacci\u00f3n; en este trabajo se estudi\u00f3 la interacci\u00f3n y se determin\u00f3 que el dominio n terminal de ing5 interacciona con el dominio iib de jade1l. La prote\u00edna ing5 se une a un p\u00e9ptido correspondiente al extremo n-terminal de la histona  h3 trimetilado en el residuo de lisina 4 con una constante de disociaci\u00f3n k d = 6.7 \u00c2\u00b1 2.3 \u00c2\u00bfm (valor medio y desviaci\u00f3n est\u00e1ndar de medidas para varios residuos). La afinidad de la interacci\u00f3n es similar a las medidas para su dominio phd aislado y tambi\u00e9n a las medidas para ing4 y su dominio phd, teniendo en cuenta las diferencias en las condiciones experimentales utilizadas. Los modelos propuestos de interacci\u00f3n para ing4 en el contexto de la cromatina, son compatibles con la estructura cristalina del d\u00edmero asim\u00e9trico de ing5.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Caracterizaci\u00f3n estructural del supresor tumoral ing5<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Caracterizaci\u00f3n estructural del supresor tumoral ing5 <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Jhon Alexander Rodriguez Buitrago <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Pa\u00eds vasco\/euskal herriko unibertsitatea<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 25\/02\/2014<\/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>Francisco Jos\u00e9 Blanco Guti\u00e9rrez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Jos\u00e9 Luis Rodriguez arrondo <\/li>\n<li>Ana rosa Viguera rincon (vocal)<\/li>\n<li>\u00f3scar Millet aguilar-galindo (vocal)<\/li>\n<li>Mar\u00eda Elena Cabez\u00f3n  navarro (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Jhon Alexander Rodriguez Buitrago Los genes de la familia de ing (inhibitors of growth) se clasifican como 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