RNF8: ¿BLANCO TERAPÉUTICO POTENCIAL PARA TRATAR EL CÁNCER DE MAMA?

Iván Anduro Corona, Humberto Astiazaran García

Resumen


El cáncer de mama hereditario se ha asociado con alteraciones en el gen BRCA1, imposibilitando a la célula tumoral reparar las lesiones de doble cadena del ADN por recombinación homóloga. En la célula normal la RH es necesaria para el mantenimiento de la integridad del ADN. Sin embargo, en las células con BRCA1 disfuncional, el ADN es reparado por el sistema de unión de extremos no homólogos propenso a errores en la0reparación del ADN. Esta condición involucra a 53BP1, cuya función es esencial para el sistema UENH, favoreciendo la inestabilidad genómica y la tumorigénesis mamaria. RNF8 es una E3 ubiquitina ligasa que promueve el enlace de BRCA1 y 53BP1 ubicándolas en los sitios de ADN dañado. Se presentan una serie de alternativas con el objetivo de reconocer y promover la eliminación de RNF8. Estas aproximaciones presentan a RNF8 como blanco en estrategias farmacológicas para eliminar la inestabilidad genómica dependiente de 53BP1 y la resistencia farmacológica promovida por la inactivación de 53BP1 en células mamarias carentes de BRCA1.


Palabras clave


53bp1; brca1; rnf8; cáncer de mama

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DOI: http://dx.doi.org/10.18633/biotecnia.v20i1.529

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