The ubiquitination of rag A GTPase by RNF152 negatively regulates mTORC1 activation.
Mol Cell
; 58(5): 804-18, 2015 Jun 04.
Article
en En
| MEDLINE
| ID: mdl-25936802
ABSTRACT
mTORC1 is essential for regulating cell growth and metabolism in response to various environmental stimuli. Heterodimeric Rag GTPases are required for amino-acid-mediated mTORC1 activation at the lysosome. However, the mechanism by which amino acids regulate Rag activation remains not fully understood. Here, we identified the lysosome-anchored E3 ubiquitin ligase RNF152 as an essential negative regulator of the mTORC1 pathway by targeting RagA for K63-linked ubiquitination. RNF152 interacts with and ubiquitinates RagA in an amino-acid-sensitive manner. The mutation of RagA ubiquitination sites abolishes this effect of RNF152 and enhances the RagA-mediated activation of mTORC1. Ubiquitination by RNF152 generates an anchor on RagA to recruit its inhibitor GATOR1, a GAP complex for Rag GTPases. RNF152 knockout results in the hyperactivation of mTORC1 and protects cells from amino-acid-starvation-induced autophagy. Thus, this study reveals a mechanism for regulation of mTORC1 signaling by RNF152-mediated K63-linked polyubiquitination of RagA.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas de Unión al GTP Monoméricas
/
Ubiquitina-Proteína Ligasas
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Complejos Multiproteicos
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Ubiquitinación
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Serina-Treonina Quinasas TOR
Límite:
Animals
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Humans
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2015
Tipo del documento:
Article
País de afiliación:
China