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p62 is a key regulator of nutrient sensing in the mTORC1 pathway.

The signaling adaptor p62 is a critical mediator of important cellular functions, owing to its ability to establish interactions with various signaling intermediaries. Here, we identify raptor as an interacting partner of p62. Thus, p62 is an integral part of the mTORC1 complex and is necessary to mediate amino acid signaling for the activation of S6K1 and 4EBP1. p62 interacts in an amino acid-dependent manner with mTOR and raptor. In addition, p62 binds the Rags proteins and favors formation of the active Rag heterodimer that is further stabilized by raptor. Interestingly, p62 colocalizes with Rags at the lysosomal compartment and is required for the interaction of mTOR with Rag GTPases in vivo and for translocation of the mTORC1 complex to the lysosome, a crucial step for mTOR activation.

Pubmed ID: 21981924

Authors

  • Duran A
  • Amanchy R
  • Linares JF
  • Joshi J
  • Abu-Baker S
  • Porollo A
  • Hansen M
  • Moscat J
  • Diaz-Meco MT

Journal

Molecular cell

Publication Data

October 7, 2011

Associated Grants

  • Agency: NCI NIH HHS, Id: P30 CA030199
  • Agency: NCI NIH HHS, Id: R01 CA132847
  • Agency: NCI NIH HHS, Id: R01 CA132847-03
  • Agency: NCI NIH HHS, Id: R01 CA134530
  • Agency: NCI NIH HHS, Id: R01 CA134530-03
  • Agency: NCI NIH HHS, Id: R01CA132847
  • Agency: NCI NIH HHS, Id: R01CA134530

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Autophagy
  • Carrier Proteins
  • Dimerization
  • GTP Phosphohydrolases
  • HEK293 Cells
  • Heat-Shock Proteins
  • Humans
  • Lysosomes
  • Mice
  • Multiprotein Complexes
  • NIH 3T3 Cells
  • Plasmids
  • Protein Kinase C
  • Proteins
  • TOR Serine-Threonine Kinases