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La expresión del gen cdc2 en la transición G1 a S en los linfocitos T humanos
Y Furukawa1, H Piwnica-Worms, T J Ernst
1Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Science (New York, N.Y.)
|November 9, 1990
Resumen
La regulación del ciclo celular involucra el producto del gen cdc2, la p34cdc2 quinasa. En las células T humanas, la expresión de cdc2 aumenta durante la transición de G1 a S, lo que requiere una inducción previa de c-myc y c-myb para la síntesis de ADN.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- Inmunología Inmunología.
Sus antecedentes:
- El producto del gen cdc2, p34cdc2, es una proteína quinasa serina-treonina clave que regula la entrada en la mitosis del ciclo celular eucariota.
- Los linfocitos T humanos en reposo (fase G0) exhiben niveles mínimos de ARN mensajero p34cdc2 y cdc2.
Objetivo del estudio:
- Investigar el papel y la regulación de p34cdc2 durante la activación de las células T y la progresión del ciclo celular.
- Para determinar la secuencia de eventos moleculares que conducen a la inducción de cdc2 en los linfocitos T.
Principales métodos:
- Análisis cuantitativo de la expresión del ARNm p34cdc2 y cdc2 en células T humanas estimuladas con fitohemaglutinina.
- Aplicación de oligodeoxinucleótidos antisense para inhibir la expresión de cdc2 y evaluar los efectos sobre la síntesis de ADN y los eventos tempranos de G1.
- Monitoreo de la expresión génica clave, incluyendo c-myb y c-myc, durante la activación de las células T.
Principales resultados:
- La estimulación de fitohemaglutinina indujo un aumento significativo en la expresión de cdc2 y el ARNm en las células T, coincidiendo con la transición de fase G1 a S.
- La inhibición antisense de la inducción de cdc2 suprimió la síntesis de ADN, pero no afectó a los eventos tempranos de G1 como la blastogénesis o la expresión del receptor.
- La inducción de la expresión de cdc2 dependía de la regulación previa hacia arriba de los proto-oncogenes c-myb y c-myc.
Conclusiones:
- La inducción de la cdc2 quinasa es un evento crítico que ocurre en la transición de G1 a S en las células T activadas.
- La regulación ascendente de cdc2 está precedida por la inducción de c-myb y c-myc, lo que indica una cascada molecular ordenada.
- Estos hallazgos esclarecen una vía reguladora específica que controla la entrada del ciclo celular en los linfocitos T humanos.
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