EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.
Blood
; 134(3): 277-290, 2019 07 18.
Article
em En
| MEDLINE
| ID: mdl-31151987
ABSTRACT
Shwachman-Diamond syndrome (SDS) is a recessive disorder typified by bone marrow failure and predisposition to hematological malignancies. SDS is predominantly caused by deficiency of the allosteric regulator Shwachman-Bodian-Diamond syndrome that cooperates with elongation factor-like GTPase 1 (EFL1) to catalyze release of the ribosome antiassociation factor eIF6 and activate translation. Here, we report biallelic mutations in EFL1 in 3 unrelated individuals with clinical features of SDS. Cellular defects in these individuals include impaired ribosomal subunit joining and attenuated global protein translation as a consequence of defective eIF6 eviction. In mice, Efl1 deficiency recapitulates key aspects of the SDS phenotype. By identifying biallelic EFL1 mutations in SDS, we define this leukemia predisposition disorder as a ribosomopathy that is caused by corruption of a fundamental, conserved mechanism, which licenses entry of the large ribosomal subunit into translation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Alongamento de Peptídeos
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Fatores de Iniciação de Peptídeos
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Ribonucleoproteína Nuclear Pequena U5
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Síndrome de Shwachman-Diamond
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Mutação
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Adolescent
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Animals
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Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article