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La proteína quinasa 2 que interactúa con el homeodominio promueve la apoptosis mediante la desregulación del
Qinghong Zhang1, Yasuhiro Yoshimatsu, Jeffrey Hildebrand
1Vollum Institute, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA. zhangq@ohsu.edu
Cell
|October 22, 2003
Resumen
El nocaut genético de CtBP (proteína de unión C-terminal) aumenta la apoptosis. La radiación UV y HIPK2 (proteína quinasa 2 que interactúa con el homeodominio) reducen los niveles de CtBP, promoviendo la apoptosis en las células deficientes en p53.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- Investigación del cáncer Investigación del cáncer.
Sus antecedentes:
- El corepresor transcripcional CtBP (proteína de unión C-terminal) juega un papel en la regulación de la expresión génica.
- El nocaut de CtBP en los fibroblastos de embriones de ratón conduce a un aumento de la apoptosis.
- Comprender la regulación de la CtBP es crucial para descifrar las vías de la apoptosis.
Objetivo del estudio:
- Identificar las vías que regulan los niveles celulares de CtBP y su papel en la apoptosis.
- Para investigar el vínculo entre CtBP, HIPK2 (proteína quinasa 2 que interactúa con el homeodominio) y la apoptosis inducida por los rayos UV.
Principales métodos:
- Cribado de una biblioteca de ADNc del embrión de ratón utilizando un complejo E1A-CtBP.
- Utilizando knockout genético, siRNA y mutantes inactivos de kinasa para estudiar la función de las proteínas.
- Evaluación de la inducción de la apoptosis en células deficientes de p53.
Principales resultados:
- HIPK2 fue identificado como una proteína que interactúa con CtBP.
- La expresión de HIPK2 o la irradiación UV redujeron los niveles de CtBP a través de la degradación mediada por proteasomas.
- La reducción de la CtBP inducida por los rayos UV dependía de la actividad de la HIPK2 quinasa.
- Los niveles reducidos de CtBP promovieron la apoptosis, incluso en las células deficientes de p53.
Conclusiones:
- Se ha esclarecido una nueva vía para la apoptosis inducida por UV que involucra la degradación de CtBP mediada por HIPK2.
- Esta vía es funcional en las células que carecen de p53, ofreciendo información sobre mecanismos apoptóticos alternativos.
- Los hallazgos destacan la regulación de la CtBP como un factor clave en la apoptosis celular.
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