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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
Intercambio de cofactores dependientes de la ubiquitinación en los factores de transcripción del homeodominio LIM
Heather P Ostendorff1, Reto I Peirano, Marvin A Peters
1Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), Universität Hamburg, Martinistrasse 85, 20251 Hamburg, Germany.
Nature
|March 8, 2002
Resumen
La proteína de unión al dominio LIM del dedo anular (RLIM) se dirige a los cofactores CLIM para la degradación, lo que permite el cambio de actividad del factor de transcripción. Este mecanismo dependiente de la ubiquitinación explica el intercambio de cofactores en la regulación génica.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Regulación genética Reglamento genético.
- Bioquímica de las proteínas Bioquímica de las proteínas
Sus antecedentes:
- Los factores de transcripción (TF) modulan la expresión génica a través de interacciones con complejos de cofactores.
- La unión del cofactor determina si las TFs activan o reprimen la transcripción génica.
- Se propone un intercambio regulado de cofactores para cambiar la actividad de TF, pero los mecanismos no están claros.
Objetivo del estudio:
- Para dilucidar los mecanismos moleculares del intercambio de cofactores en la regulación génica.
- Investigar el papel de los cofactores RLIM y CLIM en la actividad de TF LIM-HD.
- Para identificar cómo RLIM influye en la función del cofactor CLIM.
Principales métodos:
- Pruebas de la ubiquitina ligasa para evaluar la actividad enzimática del RLIM.
- Pruebas de degradación del proteasoma para monitorear la estabilidad del cofactor CLIM.
- Coinmunoprecipitación para estudiar las interacciones proteína-proteína.
Principales resultados:
- RLIM funciona como una proteína ligasa de ubiquitina dirigida a los cofactores CLIM para la degradación proteasoma.
- La ubiquitinación mediada por RLIM de los cofactores CLIM es esencial para su degradación.
- La asociación dependiente de la ubiquitinación de RLIM con las proteínas LIM-HD ocurre en presencia de cofactores CLIM.
Conclusiones:
- La degradación mediada por RLIM de los cofactores CLIM proporciona un mecanismo para el intercambio regulado de cofactores.
- Este proceso permite cambiar la actividad del factor de transcripción LIM-HD entre la represión y la activación.
- Los hallazgos sugieren un mecanismo general para la regulación de la transcripción a través del intercambio de cofactores.
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