RB1CC1 protein positively regulates transforming growth factor-beta signaling through the modulation of Arkadia E3 ubiquitin ligase activity.
J Biol Chem
; 286(37): 32502-12, 2011 Sep 16.
Article
en En
| MEDLINE
| ID: mdl-21795712
ABSTRACT
Transforming growth factor-ß (TGF-ß) signaling is controlled by a variety of regulators, of which Smad7, c-Ski, and SnoN play a pivotal role in its negative regulation. Arkadia is a RING-type E3 ubiquitin ligase that targets these negative regulators for degradation to enhance TGF-ß signaling. In the present study we identified a candidate human tumor suppressor gene product RB1CC1/FIP200 as a novel positive regulator of TGF-ß signaling that functions as a substrate-selective cofactor of Arkadia. Overexpression of RB1CC1 enhanced TGF-ß signaling, and knockdown of endogenous RB1CC1 attenuated TGF-ß-induced expression of target genes as well as TGF-ß-induced cytostasis. RB1CC1 down-regulated the protein levels of c-Ski but not SnoN by enhancing the activity of Arkadia E3 ligase toward c-Ski. Substrate selectivity is primarily attributable to the physical interaction of RB1CC1 with substrates, suggesting its role as a scaffold protein. RB1CC1 thus appears to play a unique role as a modulator of TGF-ß signaling by restricting substrate specificity of Arkadia.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Tirosina Quinasas
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Proteínas Nucleares
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Transducción de Señal
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Regulación de la Expresión Génica
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Factor de Crecimiento Transformador beta
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Ubiquitina-Proteína Ligasas
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Péptidos y Proteínas de Señalización Intracelular
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2011
Tipo del documento:
Article
País de afiliación:
Japón