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COP1 es un supresor tumoral que causa la degradación de los factores de transcripción ETS
Alberto C Vitari1, Kevin G Leong, Kim Newton
1Department of Physiological Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Nature
|May 17, 2011
Resumen
La ubiquitina ligasa COP1 (también conocida como RFWD2) actúa como supresor tumoral al degradar ETV1, ETV4 y ETV5. Su pérdida promueve el desarrollo y la invasividad del cáncer de próstata.
Área de la Ciencia:
- Oncología Oncología.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- Los proto-oncogenes ETV1, ETV4 y ETV5 se alteran con frecuencia en el cáncer de próstata.
- Su regulación post-traducional, crucial para el desarrollo, se entiende mal.
Objetivo del estudio:
- Para identificar a los reguladores de ETV1, ETV4 y ETV5.
- Para investigar el papel de COP1 en el cáncer de próstata.
Principales métodos:
- Pruebas de ubiquitinación para evaluar la degradación de ETV1 para el COP1.
- Análisis de las translocaciones del cáncer de próstata (TMPRSS2:ETV1) para motivos vinculantes de la COP1.
- Deficiencia COP1 específica de la próstata en modelos de ratón.
- Análisis de muestras de cáncer de próstata humano para las alteraciones COP1 y ETV1.
Principales resultados:
- COP1 ubicuita y degrada ETV1, ETV4 y ETV5.
- Las translocaciones del cáncer de próstata crean variantes de ETV1 insensibles a COP1.
- La deficiencia de COP1 en ratones aumenta los niveles de ETV1, lo que lleva a la hiperplasia y las lesiones pre-neoplásicas.
- La pérdida de COP1 y PTEN aumenta la invasividad del adenocarcinoma de próstata.
- Los cánceres de próstata humanos muestran pérdida de COP1 y ETV1.1 elevado.
Conclusiones:
- COP1 es un supresor de tumores que regula negativamente ETV1, ETV4 y ETV5.
- La regulación a la baja de COP1 promueve la proliferación de células epiteliales de la próstata y la tumorigénesis.
- La inactivación de COP1, a través de la translocación o pérdida de genes, confiere una ventaja selectiva en el desarrollo del cáncer de próstata.
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