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TOR para mamíferos: es un sensor homeostático de ATP
P B Dennis1, A Jaeschke, M Saitoh
1The Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058, Basel, Switzerland.
Science (New York, N.Y.)
|November 3, 2001
Resumen
La rapamicina, un medicamento contra el cáncer, se dirige a los tumores sólidos. Los investigadores descubrieron que la vía Target of Rapamycin (mTOR) de los mamíferos detecta los niveles de energía celular (ATP), no solo los aminoácidos, lo que afecta el crecimiento del cáncer.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Investigación de Investigación del Cáncer.
Sus antecedentes:
- La rapamicina es un agente anticancerígeno eficaz para los tumores sólidos.
- El crecimiento de tumores sólidos, especialmente en hipoxia, depende del suministro de nutrientes y mitógenos.
- El objetivo mamífero de la rapamicina (mTOR) regula la biogénesis del ribosoma y el crecimiento celular en respuesta a la disponibilidad de nutrientes, particularmente aminoácidos.
Objetivo del estudio:
- Investigar los mecanismos reguladores de la vía mTOR en respuesta al cambio de las concentraciones de nutrientes.
- Para determinar si la regulación de la vía mTOR está influenciada por los niveles intracelulares de ATP independientemente de la abundancia de aminoácidos.
- Para identificar el mTOR como un sensor directo de la concentración de ATP celular.
Principales métodos:
- Investigó la influencia de la concentración intracelular de ATP en la vía mTOR.
- Examinó el papel de la abundancia de aminoácidos en la regulación de la vía mTOR.
- Evaluó las capacidades de detección directa de mTOR para ATP.
Principales resultados:
- La actividad de la vía mTOR está modulada por la concentración intracelular de ATP.
- Esta regulación dependiente del ATP ocurre independientemente de los niveles de aminoácidos.
- mTOR funciona como un sensor directo del ATP intracelular.
Conclusiones:
- La vía mamífera objetivo de la rapamicina (mTOR) es sensible al estado energético celular (ATP).
- mTOR actúa como un sensor de ATP, integrando las señales de energía en la regulación del crecimiento.
- Este hallazgo proporciona nuevos conocimientos sobre el metabolismo del cáncer y las estrategias terapéuticas dirigidas a mTOR.
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