Cullin-3-RING ubiquitin ligase activity is required for striated muscle function in mice.
J Biol Chem
; 293(23): 8802-8811, 2018 06 08.
Article
em En
| MEDLINE
| ID: mdl-29653945
ABSTRACT
Control of protein homeostasis is an essential cellular process that, when perturbed, can result in the deregulation or toxic accumulation of proteins. Owing to constant mechanical stress, striated muscle proteins are particularly prone to wear and tear and require several protein quality-control mechanisms to coordinate protein turnover and removal of damaged proteins. Kelch-like proteins, substrate adapters for the Cullin-3 (Cul3)-RING ligase (CRL3) complex, are emerging as critical regulators of striated muscle development and function, highlighting the importance of Cul3-mediated proteostasis in muscle function. To explore the role of Cul3-mediated proteostasis in striated muscle, here we deleted Cul3 specifically in either skeletal muscle (SkM-Cul3 KO) or cardiomyocytes (CM-Cul3 KO) of mice. The loss of Cul3 caused neonatal lethality and dramatic alterations in the proteome, which were unique to each striated muscle type. Many of the proteins whose expression was significantly changed in the SkM-Cul3 KO were components of the extracellular matrix and sarcomere, whereas proteins altered in the CM-Cul3 KO were involved in metabolism. These findings highlight the requirement for striated muscle-specific CRL3 activity and indicate how the CRL3 complex can control different nodes of protein interaction networks in different types of striated muscle. Further identification of Cul3 substrates, and how these substrates are targeted, may reveal therapeutic targets and treatment regimens for striated muscle diseases.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Deleção de Genes
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Miócitos Cardíacos
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Proteínas Culina
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Músculo Estriado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2018
Tipo de documento:
Article