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Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
Una red de empalme alternativa vincula el control del ciclo celular con la apoptosis
Michael J Moore1, Qingqing Wang, Caleb J Kennedy
1Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|August 14, 2010
Resumen
El empalme alternativo regula la muerte celular y se interrumpe en enfermedades. Este estudio revela una red que vincula el control del ciclo celular a la apoptosis a través del empalme alternativo de genes clave.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- Genética La genética.
Sus antecedentes:
- El empalme alternativo es un mecanismo clave para la regulación biológica y la diversidad.
- La desregulación del empalme alternativo está implicada en varias enfermedades, incluido el cáncer.
- La familia Bcl2 de factores de apoptosis juega un papel crítico en la muerte celular programada.
Objetivo del estudio:
- Investigar el control global del empalme alternativo en las células humanas.
- Identificar los reguladores del empalme alternativo para el ARNm Bcl-x y Mcl1.
- Comprender el vínculo entre el control del ciclo celular y la apoptosis a través del empalme.
Principales métodos:
- Pantalla de siRNA de todo el genoma para identificar los reguladores de empalme.
- Análisis de los patrones de empalme de ARNm para los factores de apoptosis de la familia Bcl2.
- Investigación del papel de los factores del ciclo celular y la aurora cinasa A. Investigación del papel de los factores del ciclo celular y la aurora cinasa A.
Principales resultados:
- Se identificó una red de factores del ciclo celular, incluida la aurora quinasa A, como reguladores del empalme de Bcl-x y Mcl1.
- La detención mitótica inducida por fármacos o siRNAs promovió el empalme proapoptótico de Bcl-x, Mcl1 y caspase-9.
- La rotación post-traducional del regulador de empalme ASF/SF2 se correlacionó con cambios en las variantes de empalme, impactando la apoptosis.
Conclusiones:
- Una nueva red de empalme alternativa enlaza el control del ciclo celular con la apoptosis.
- La regulación coordinada al alza de las variantes de empalme de la muerte promueve la apoptosis en las células sometidas a una detención mitótica.
- El regulador de empalme ASF/SF2 juega un papel global en la regulación de la apoptosis a través del empalme alternativo.
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