USP15 targets ALK3/BMPR1A for deubiquitylation to enhance bone morphogenetic protein signalling.
Open Biol
; 4(5): 140065, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24850914
ABSTRACT
Protein kinase ALK3/BMPR1A mediates bone morphogenetic protein (BMP) signalling through phosphorylation and activation of SMADs 1/5/8. SMAD6, a transcriptional target of BMP, negatively regulates the BMP pathway by recruiting E3 ubiquitin ligases and targeting ALK3 for ubiquitin-mediated degradation. Here, we identify a deubiquitylating enzyme USP15 as an interactor of SMAD6 and ALK3. We show that USP15 enhances BMP-induced phosphorylation of SMAD1 by interacting with and deubiquitylating ALK3. RNAi-mediated depletion of USP15 increases ALK3 K48-linked polyubiquitylation, and reduces both BMP-induced SMAD1 phosphorylation and transcription of BMP target genes. We also show that loss of USP15 expression from mouse myoblast cells inhibits BMP-induced osteoblast differentiation. Furthermore, USP15 modulates BMP-induced phosphorylation of SMAD1 and transcription during Xenopus embryogenesis.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Xenopus laevis
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Proteínas Morfogenéticas Ósseas
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Proteínas de Xenopus
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Receptores de Proteínas Morfogenéticas Ósseas Tipo I
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Proteína Smad1
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Proteases Específicas de Ubiquitina
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article