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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Una vía común E2F-1 y p73 media la muerte celular inducida por la activación de TCR
N A Lissy1, P K Davis, M Irwin
1Howard Hughes Medical Institute, Department of Pathology, Washington University School of Medicine, St Louis Missouri 63110, USA.
Nature
|October 18, 2000
Resumen
La activación del receptor de células T desencadena la apoptosis a través de E2F-1 y p73, no p53. Este proceso, crucial para la regulación de las células T, implica un punto de control tardío del ciclo celular G1, destacando p73.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- La estimulación del receptor de células T (TCR) en las células T periféricas ciclistas induce la apoptosis, conocida como muerte celular inducida por activación de TCR (TCR-AICD).
- La TCR-AICD ocurre independientemente de la proteína supresora de tumores p53 e involucra un punto de control tardío del ciclo celular G1.
- El factor de transcripción E2F-1, un inductor de la apoptosis, juega un papel en el número de células T, ya que su interrupción conduce a un aumento de las poblaciones de células T y a la esplenomegalia.
Objetivo del estudio:
- Investigar los mecanismos moleculares subyacentes a la muerte celular inducida por la activación de TCR (TCR-AICD).
- Determinar las funciones de E2F-1 y p73 en la apoptosis mediada por TCR.
- Para aclarar el punto de control del ciclo celular involucrado en TCR-AICD.
Principales métodos:
- Análisis de la expresión génica en células T sometidas a TCR-AICD.
- Introducción de las proteínas negativas dominantes (E2F-1, p73, E2F-2, E2F-4, p53) en las células T.
- Evaluación de la apoptosis mediada por TCR en las células T primarias con gen nulo (E2F-1-nulo, p73-nulo).
Principales resultados:
- Las células T sometidas a TCR-AICD inducen el gen relacionado con p53, p73.
- Las proteínas dominantes negativas E2F-1 o p73 protegieron a las células T de la apoptosis mediada por TCR, mientras que las dominantes negativas E2F-2, E2F-4 o p53 no lo hicieron.
- Las células T primarias E2F-1-nulo o p73-nulo no se sometieron a apoptosis mediada por TCR.
Conclusiones:
- TCR-AICD ocurre desde un punto de control del ciclo celular G1 tardío dependiente tanto de las actividades de E2F-1 como de p73.
- A diferencia de p53, p73 integra estímulos apoptóticos mediados por el receptor.
- Estos hallazgos revelan una nueva vía para regular la apoptosis de las células T.
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