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

Mol Cell. 2011 Oct 7;44(1):134-46. doi: 10.1016/j.molcel.2011.06.038.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Autophagy
  • Carrier Proteins / metabolism
  • Dimerization
  • GTP Phosphohydrolases / metabolism
  • HEK293 Cells
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lysosomes / metabolism
  • Mechanistic Target of Rapamycin Complex 1
  • Mice
  • Multiprotein Complexes
  • NIH 3T3 Cells
  • Plasmids / metabolism
  • Protein Kinase C / metabolism
  • Proteins / metabolism*
  • Regulatory-Associated Protein of mTOR
  • Sequestosome-1 Protein
  • TOR Serine-Threonine Kinases

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Heat-Shock Proteins
  • Intracellular Signaling Peptides and Proteins
  • Multiprotein Complexes
  • Nbr1 protein, mouse
  • Proteins
  • Regulatory-Associated Protein of mTOR
  • Rptor protein, mouse
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Sqstm1 protein, mouse
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • Protein Kinase C
  • GTP Phosphohydrolases