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La quinasa humana VRK1 regula la estabilidad de los Cuerpos de Cajal protegiendo a Coilina de su degradación en el proteasoma

Authors: Cantarero, Lara; Sanz-García, Marta; Lazo, Pedro A.;

La quinasa humana VRK1 regula la estabilidad de los Cuerpos de Cajal protegiendo a Coilina de su degradación en el proteasoma

Abstract

Los Cuerpos de Cajal (CB) son suborgánulos nucleares implicados en el procesamiento del RNA, importante en el proceso de splicing. El ensamblaje de los CB, junto con su proteína scaffold Coilina, se regula a través del ciclo celular. La quinasa humana VRK1, la actividad de la cual también es regulada dependiendo del ciclo celular, interacciona y fosforila a Coilina en el residuo serina 184, regulando la estabilidad de los CB. Así, el silenciamiento de esta quinasa, o la falta de suero en el medio, inactivan a VRK1 causando una pérdida en la fosforilación de Coilina y provocando el desensamblaje de estos suborgánulos nucleares; efecto rescatado por una VRK1 activa pero no por la quinasa inactiva. La pérdida de fosforilación de Coilina y posterior desensamblaje de los CB, son recuperados por los inhibidores del proteasoma. La falta de VRK1 provoca la ubiquitinación, a través de la lisina 48, de Coilina en el núcleo. Este proceso es mediado en parte por Mdm2, y el exporte al citosol para su degradación en el proteasoma; de tal forma que este proceso se interrumpe al inhibir el exporte nuclear con LeptomicinaB. De este modo, VRK1 protege a Coilina de su degradación y es una quinasa esencial para el mantenimiento de la estructura de los Cuerpos de Cajal y su regulación en el ciclo celular.

Resumen del póster presentado al XXXVII Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Granada (España) del 9 al 12 de septiembre de 2014.

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selected citations
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This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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