Gene interactions and pathways from curated databases and text-mining
Mol Biol Cell 2009, PMID: 19225151

ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery.

Jung, Chang Hwa; Jun, Chang Bong; Ro, Seung-Hyun; Kim, Young-Mi; Otto, Neil Michael; Cao, Jing; Kundu, Mondira; Kim, Do-Hyung

Autophagy, the starvation-induced degradation of bulky cytosolic components, is up-regulated in mammalian cells when nutrient supplies are limited. Although mammalian target of rapamycin (mTOR) is known as the key regulator of autophagy induction, the mechanism by which mTOR regulates autophagy has remained elusive. Here, we identify that mTOR phosphorylates a mammalian homologue of Atg13 and the mammalian Atg1 homologues ULK1 and ULK2. The mammalian Atg13 binds both ULK1 and ULK2 and mediates the interaction of the ULK proteins with FIP200. The binding of Atg13 stabilizes and activates ULK and facilitates the phosphorylation of FIP200 by ULK, whereas knockdown of Atg13 inhibits autophagosome formation. Inhibition of mTOR by rapamycin or leucine deprivation, the conditions that induce autophagy, leads to dephosphorylation of ULK1, ULK2, and Atg13 and activates ULK to phosphorylate FIP200. These findings demonstrate that the ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in response to mTOR signaling.

Document information provided by NCBI PubMed

Text Mining Data

mTOR signaling → ULK-Atg13-FIP200: " ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery "

mTOR signaling → ULK-Atg13-FIP200: " ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery "

mTOR signaling → ULK-Atg13-FIP200: " ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery "

FIP200 → Atg13: " The mammalian Atg13 binds both ULK1 and ULK2 and mediates the interaction of the ULK proteins with FIP200 "

ULK → Atg13: " The binding of Atg13 stabilizes and activates ULK and facilitates the phosphorylation of FIP200 by ULK, whereas knockdown of Atg13 inhibits autophagosome formation "

ULK ⊣ mTOR: " Inhibition of mTOR by rapamycin or leucine deprivation, the conditions that induce autophagy, leads to dephosphorylation of ULK1, ULK2, and Atg13 and activates ULK to phosphorylate FIP200 "

ULK-Atg13-FIP200 → mTOR signaling: " These findings demonstrate that the ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in response to mTOR signaling "

ULK-Atg13-FIP200 → mTOR signaling: " These findings demonstrate that the ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in response to mTOR signaling "

ULK-Atg13-FIP200 → mTOR signaling: " These findings demonstrate that the ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in response to mTOR signaling "

Manually curated Databases

  • IRef Innatedb Interaction: ATG13 — MTOR (unknown, -)
  • IRef Innatedb Interaction: MTOR — 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