ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy.
J Biol Chem
; 284(18): 12297-305, 2009 May 01.
Article
en En
| MEDLINE
| ID: mdl-19258318
ABSTRACT
Autophagy is a degradative process that recycles long-lived and faulty cellular components. It is linked to many diseases and is required for normal development. ULK1, a mammalian serine/threonine protein kinase, plays a key role in the initial stages of autophagy, though the exact molecular mechanism is unknown. Here we report identification of a novel protein complex containing ULK1 and two additional protein factors, FIP200 and ATG13, all of which are essential for starvation-induced autophagy. Both FIP200 and ATG13 are critical for correct localization of ULK1 to the pre-autophagosome and stability of ULK1 protein. Additionally, we demonstrate by using both cellular experiments and a de novo in vitro reconstituted reaction that FIP200 and ATG13 can enhance ULK1 kinase activity individually but both are required for maximal stimulation. Further, we show that ATG13 and ULK1 are phosphorylated by the mTOR pathway in a nutrient starvation-regulated manner, indicating that the ULK1.ATG13.FIP200 complex acts as a node for integrating incoming autophagy signals into autophagosome biogenesis.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Autofagia
/
Proteínas Tirosina Quinasas
/
Transducción de Señal
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Proteínas Portadoras
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Proteínas Serina-Treonina Quinasas
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Fosfotransferasas (Aceptor de Grupo Alcohol)
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Péptidos y Proteínas de Señalización Intracelular
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Proteínas Adaptadoras Transductoras de Señales
/
Complejos Multienzimáticos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos