Ubiquitination of hnRNPA1 by TRAF6 links chronic innate immune signaling with myelodysplasia.
Nat Immunol
; 18(2): 236-245, 2017 02.
Article
em En
| MEDLINE
| ID: mdl-28024152
ABSTRACT
Toll-like receptor (TLR) activation contributes to premalignant hematologic conditions, such as myelodysplastic syndromes (MDS). TRAF6, a TLR effector with ubiquitin (Ub) ligase activity, is overexpressed in MDS hematopoietic stem/progenitor cells (HSPCs). We found that TRAF6 overexpression in mouse HSPC results in impaired hematopoiesis and bone marrow failure. Using a global Ub screen, we identified hnRNPA1, an RNA-binding protein and auxiliary splicing factor, as a substrate of TRAF6. TRAF6 ubiquitination of hnRNPA1 regulated alternative splicing of Arhgap1, which resulted in activation of the GTP-binding Rho family protein Cdc42 and accounted for hematopoietic defects in TRAF6-expressing HSPCs. These results implicate Ub signaling in coordinating RNA processing by TLR pathways during an immune response and in premalignant hematologic diseases, such as MDS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Pré-Cancerosas
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Síndromes Mielodisplásicas
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Células-Tronco Hematopoéticas
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Transdução de Sinais
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Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B
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Fator 6 Associado a Receptor de TNF
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Ubiquitinação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article