The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis.
Cancer Cell
; 17(6): 609-21, 2010 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-20541477
ABSTRACT
MLL is involved in chromosomal rearrangements that generate fusion proteins with deregulated transcriptional activity. The mechanisms of MLL fusion protein-mediated transcriptional activation are poorly understood. Here we show MLL interacts directly with the polymerase associated factor complex (PAFc) through sequences flanking the CxxC domain. PAFc interacts with RNA polymerase II and stimulates posttranslational histone modifications. PAFc augments MLL and MLL-AF9 mediated transcriptional activation of Hoxa9. Conversely, knockdown of PAFc disrupts MLL fusion protein-mediated transcriptional activation and MLL recruitment to target loci. PAFc gene expression is downregulated during hematopoiesis and likely serves to regulate MLL function. Deletions of MLL that abolish interactions with PAFc also eliminate MLL-AF9 mediated immortalization indicating an essential function for this interaction in leukemogenesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
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Leucemia
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Proteínas de Transporte
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Proteínas de Fusão Oncogênica
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Transformação Celular Neoplásica
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Proteínas de Homeodomínio
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Proteína de Leucina Linfoide-Mieloide
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article