The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures.
Leukemia
; 25(1): 135-44, 2011 Jan.
Article
en En
| MEDLINE
| ID: mdl-21030982
Expression of the AF4-MLL fusion protein in murine hematopoietic progenitor/stem cells results in the development of proB acute lymphoblastic leukemia. In this study, we affinity purified the AF4-MLL and AF4 protein complexes to elucidate their function. We observed that the AF4 complex consists of 11 binding partners and exhibits positive transcription elongation factor b (P-TEFb)-mediated activation of promoter-arrested RNA polymerase (pol) II in conjunction with several chromatin-modifying activities. In contrast, the AF4-MLL complex consists of at least 16 constituents including P-TEFb kinase, H3K4(me3) and H3K79(me3) histone methyltransferases (HMT), a protein arginine N-methyltransferase and a histone acetyltransferase. These findings suggest that the AF4-MLL protein disturbs the fine-tuned activation cycle of promoter-arrested RNA Pol II and causes altered histone methylation signatures. Thus, we propose that these two processes are key to trigger cellular reprogramming that leads to the onset of acute leukemia.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Leucemia
/
Proteínas de Fusión Oncogénica
/
Factor B de Elongación Transcripcional Positiva
/
Epigénesis Genética
/
Proteínas de Unión al ADN
/
Proteína de la Leucemia Mieloide-Linfoide
Tipo de estudio:
Etiology_studies
Límite:
Humans
Idioma:
En
Revista:
Leukemia
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Reino Unido