DEPTOR
Function
Negative regulator of the mTORC1 and mTORC2 complexes: inhibits the protein kinase activity of MTOR, thereby inactivating both complexes (PubMed:19446321, PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:25936805, PubMed:29382726, PubMed:34519268, PubMed:34519269). DEPTOR inhibits mTORC1 and mTORC2 to induce autophagy (PubMed:22017875, PubMed:22017876, PubMed:22017877). In contrast to AKT1S1/PRAS40, only partially inhibits mTORC1 activity (PubMed:34519268, PubMed:34519269).
Post-translational modifications
Phosphorylation weakens interaction with MTOR within mTORC1 and mTORC2 (PubMed:19446321). Phosphorylated at Ser-286, Ser-287 and Ser-291 in response to mitogenic stimulation by MTOR: DEPTOR is either directly phosphorylated by MTOR or indirectly via proteins kinases that are activated by MTOR, such as CK1/CSNK1A1 (PubMed:22017875, PubMed:22017876, PubMed:22017877). Phosphorylation at Ser-286, Ser-287 and Ser-291 promotes ubiquitination by the SCF(BTRC) complex, followed by degradation (PubMed:22017875, PubMed:22017876, PubMed:22017877). Phosphorylation at Ser-235 by MAPK3/ERK1 promotes deubiquitination by USP7, enhancing its stability (PubMed:35216969). Phosphorylation at Tyr-289 by SYK impairs its interaction with MTOR, promoting mTORC1 and mTORC2 signaling (PubMed:34634301).
Ubiquitinated; leading to proteasomal degradation (PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:30080879, PubMed:33110214). Ubiquitination by the SCF(BTRC) and SCF(FBXW11) complexes following phosphorylation at Ser-286, Ser-287 and Ser-291 by MTOR, leads to its degradation by the proteasome (PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:33110214). Deubiquitinated by OTUB1 in response to amino acid via a non-canonical mechanism, leading to DEPTOR stability (PubMed:29382726). Deubiquitinated by USP7 following phosphorylation at Ser-235, promoting its stability (PubMed:35216969).
Cellular localization
- Lysosome membrane
- Localizes to the lysosomal membrane when associated with the mTORC1 and mTORC2 complexes.
Alternative names
DEPDC6, DEPTOR, DEP domain-containing mTOR-interacting protein, hDEPTOR, DEP domain-containing protein 6