Gene interactions and pathways from curated databases and text-mining
Mol Biol Cell 2009, PMID: 19211835

Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy.

Hosokawa, Nao; Hara, Taichi; Kaizuka, Takeshi; Kishi, Chieko; Takamura, Akito; Miura, Yutaka; Iemura, Shun-ichiro; Natsume, Tohru; Takehana, Kenji; Yamada, Naoyuki; Guan, Jun-Lin; Oshiro, Noriko; Mizushima, Noboru

Autophagy is an intracellular degradation system, by which cytoplasmic contents are degraded in lysosomes. Autophagy is dynamically induced by nutrient depletion to provide necessary amino acids within cells, thus helping them adapt to starvation. Although it has been suggested that mTOR is a major negative regulator of autophagy, how it controls autophagy has not yet been determined. Here, we report a novel mammalian autophagy factor, Atg13, which forms a stable approximately 3-MDa protein complex with ULK1 and FIP200. Atg13 localizes on the autophagic isolation membrane and is essential for autophagosome formation. In contrast to yeast counterparts, formation of the ULK1-Atg13-FIP200 complex is not altered by nutrient conditions. Importantly, mTORC1 is incorporated into the ULK1-Atg13-FIP200 complex through ULK1 in a nutrient-dependent manner and mTOR phosphorylates ULK1 and Atg13. ULK1 is dephosphorylated by rapamycin treatment or starvation. These data suggest that mTORC1 suppresses autophagy through direct regulation of the approximately 3-MDa ULK1-Atg13-FIP200 complex.

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Text Mining Data

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Manually curated Databases

  • IRef Innatedb Interaction: ATG13 — MTOR (unknown, -)
  • NCI Pathway Database mTOR signaling pathway: mTORC1 complex (MTOR-MLST8-RPTOR) → mTORC1/ULK1-2/ATG13/FIP200 complex (MTOR-MLST8-RPTOR-ULK1_ULK2-ATG13-RB1CC1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC1 complex (MTOR-MLST8-RPTOR) → ULK1-2/ATG13/FIP200 complex (ULK1_ULK2-ATG13-RB1CC1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC1/ULK1-2/ATG13/FIP200 complex (MTOR-MLST8-RPTOR-ULK1_ULK2-ATG13-RB1CC1) → ULK1-2/ATG13/FIP200 complex (ULK1_ULK2-ATG13-RB1CC1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
In total, 28 gene pairs are associated to this article in curated databases