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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Regulación de la función específica de unión al ADN de la p53
T R Hupp1, D W Meek, C A Midgley
1Cancer Research Campaign Laboratories, Department of Biochemistry, University of Dundee, Scotland.
Cell
|November 27, 1992
Resumen
La proteína supresora de tumores p53 tiene una actividad oculta de unión al ADN crucial para su función. Esta actividad críptica puede ser desbloqueada por factores celulares, potencialmente regulando el crecimiento celular y la supresión tumoral.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Investigación del cáncer Investigación del cáncer.
- Bioquímica de las proteínas Bioquímica de las proteínas
Sus antecedentes:
- La proteína supresora de tumores p53 juega un papel crítico en la prevención del cáncer.
- Su actividad de unión al ADN es esencial para su función supresora de tumores.
- Se ha observado que esta actividad de unión al ADN en p53 es críptica o latente.
Objetivo del estudio:
- Investigar los mecanismos que regulan la actividad de unión al ADN críptico de p53.
- Para identificar los factores y condiciones celulares que pueden activar la unión al ADN p53.
- Comprender las implicaciones de la activación de la unión al ADN p53 para la supresión tumoral.
Principales métodos:
- Utilizó ensayos de desplazamiento de la movilidad del gel para evaluar la unión al ADN.
- Empleado p53 humano recombinante de tipo salvaje y un anticuerpo monoclonal.
- Investigó los efectos de las modificaciones del terminal C, la proteólisis, el dnaK de E. coli y la caseína quinasa II en la unión del ADN p53.
Principales resultados:
- El p53 humano de tipo salvaje recombinante exhibió una unión débil al ADN específica de la secuencia.
- Un anticuerpo monoclonal dirigido al extremo C activó estequiométricamente la unión al ADN críptico de p53.
- La activación también se logró a través de la deleción C-terminal, proteólisis leve, E. coli dnaK y fosforilación mediada por caseína quinasa II.
Conclusiones:
- La actividad de unión al ADN p53 está regulada por su dominio C-terminal y puede ser activada por varios mecanismos celulares.
- La activación de la unión al ADN p53 por factores celulares es probablemente crítica para sus funciones supresoras de tumores, incluida la detención del crecimiento celular.
- Comprender estos mecanismos reguladores proporciona información sobre el papel de la p53 en la prevención del cáncer.
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