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Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates
Published on: February 27, 2016
hSIR2 ((SIRT1) funciona como una desacetilasa p53 dependiente de NAD
H Vaziri1, S K Dessain, E Ng Eaton
1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Cell
|October 24, 2001
Resumen
El gen humano hSIR2 (SIRT1) desacetila la proteína y inhibe el supresor tumoral p53. Esta desacetilación regula el p53.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- El daño al ADN desencadena la acetilación de p53, lo que lleva a la detención del crecimiento celular o a la apoptosis.
- La proteína hSIR2 (SIRT1), un homólogo humano de la levadura Sir2, está implicada en el envejecimiento y la respuesta al daño del ADN.
Objetivo del estudio:
- Para investigar el papel de hSIR2 (SIRT1) en la regulación de la actividad de la proteína p53.
- Para determinar si hSIR2 (SIRT1) interactúa directamente con y modifica p53.
Principales métodos:
- Estudió la interacción entre hSIR2 (SIRT1) y p53 en células humanas.
- Se evaluó el efecto del hSIR2 de tipo silvestre y catalíticamente inactivo (SIRT1) en la actividad transcripcional de p53.
- Se midió la apoptosis dependiente de p53 y la radiosensibilidad.
Principales resultados:
- hSIR2 (SIRT1) se une y desacetila p53, específicamente en el residuo C-terminal de Lys382.
- La expresión de hSIR2 de tipo salvaje (SIRT1) reduce la actividad transcripcional de p53.
- La hSIR2 inactiva (SIRT1) mejora la apoptosis dependiente de p53 y la radiosensibilidad.
Conclusiones:
- hSIR2 (SIRT1) regula negativamente la función de p53 a través de la desacetilación.
- SIRT1 juega un papel crítico en la vía de respuesta al daño del ADN mediante la modulación de la actividad de p53.
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