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La fosforilación apoptótica de la histona H2B está mediada por la veinte quinasa estéril de mamíferos
Wang L Cheung1, Kozo Ajiro, Kumiko Samejima
1Department of Microbiology, University of Virginia Health System, Charlottesville 22908, USA.
Cell
|May 22, 2003
Resumen
La muerte celular programada implica modificaciones de las histonas. Los investigadores encontraron que la fosforilación de la histona H2B en la serina 14 está relacionada con la apoptosis, regulada por la quinasa Mst1 escindida por caspase.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- El ADN eucariótico se asocia con las proteínas histonas, influyendo en la estructura de la cromatina.
- Las señales distintivas de la apoptosis, como la condensación de cromatina, pueden ser moduladas por modificaciones de histonas post-traducionales.
Objetivo del estudio:
- Para investigar el papel de las modificaciones histónicas en la apoptosis.
- Para identificar la modificación específica de la histona y la quinasa responsable de ella durante la muerte celular programada.
Principales métodos:
- Análisis correlativo de la fosforilación de la histona H2B en la serina 14 (S14) con apoptosis en células de vertebrados.
- Identificación y caracterización de la actividad de la quinasa H2B S14 en las células apoptóticas.
- Ensayos de fosforilación in vitro e in vivo utilizando la quinasa Mst1 y la histona H2B.
Principales resultados:
- La fosforilación de la histona H2B en S14 se observó en células sometidas a apoptosis en varias especies de vertebrados.
- Se encontró que una 34 kDa quinasa, identificada como caspase-cleaved mamífero estéril veinte (Mst1) quinasa, induce la fosforilación H2B en S14.
- La fosforilación de H2B S14 dependía de la escisión de Mst1 por caspase-3, lo que indica un vínculo directo con las vías apoptóticas.
Conclusiones:
- La fosforilación de la histona H2B en S14 es una modificación conservada asociada con la cromatina apoptótica.
- La Mst1 quinasa escindida por caspase es un regulador clave de esta modificación específica de la histona durante la apoptosis.
- Estos hallazgos sugieren un nuevo mecanismo en la muerte celular programada y proponen un potencial "código de histona apoptótica".
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