Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state.
Cell
; 150(3): 563-74, 2012 Aug 03.
Article
en En
| MEDLINE
| ID: mdl-22863009
ABSTRACT
Myc oncoproteins directly regulate transcription by binding to target genes, yet this only explains a fraction of the genes affected by Myc. mRNA turnover is controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs) found within many transcripts. Analyses of precancerous and malignant Myc-expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED) genes and select AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also operational during B lymphopoiesis and IL7 signaling. Importantly, TTP suppression is a hallmark of cancers with MYC involvement, and restoring TTP impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant state. Further, there is a selection for TTP loss in malignancy; thus, TTP functions as a tumor suppressor. Finally, Myc/TTP-directed control of select cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc targets AUBPs to regulate ARED genes that control tumorigenesis.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Genes Supresores de Tumor
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Linfoma de Células B
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Proteínas Proto-Oncogénicas c-myc
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Tristetraprolina
Límite:
Animals
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Humans
Idioma:
En
Año:
2012
Tipo del documento:
Article