The Eya1 phosphatase promotes Shh signaling during hindbrain development and oncogenesis.
Dev Cell
; 33(1): 22-35, 2015 Apr 06.
Article
em En
| MEDLINE
| ID: mdl-25816987
ABSTRACT
Sonic hedgehog (Shh) signaling is critical in development and oncogenesis, but the mechanisms regulating this pathway remain unclear. Although protein phosphorylation clearly affects Shh signaling, little is known about phosphatases governing the pathway. Here, we conducted a small hairpin RNA (shRNA) screen of the phosphatome and identified Eya1 as a positive regulator of Shh signaling. We find that the catalytically active phosphatase Eya1 cooperates with the DNA-binding protein Six1 to promote gene induction in response to Shh and that Eya1/Six1 together regulate Gli transcriptional activators. We show that Eya1, which is mutated in a human deafness disorder, branchio-oto-renal syndrome, is critical for Shh-dependent hindbrain growth and development. Moreover, Eya1 drives the growth of medulloblastoma, a Shh-dependent hindbrain tumor. Together, these results identify Eya1 and Six1 as key components of the Shh transcriptional network in normal development and in oncogenesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rombencéfalo
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Proteínas Nucleares
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Proteínas Tirosina Fosfatases
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Receptores de Superfície Celular
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Proteínas de Homeodomínio
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Peptídeos e Proteínas de Sinalização Intracelular
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Fatores de Transcrição Kruppel-Like
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Proteínas Hedgehog
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Carcinogênese
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Meduloblastoma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Dev Cell
Ano de publicação:
2015
Tipo de documento:
Article