Dock7 regulates AKT and mTOR/S6K activity required for the transformed phenotypes and survival of cancer cells
Teran, O. Y.; Zanotelli, M. R.; Lin, M.-c. J.; Cerione, R. A.; Wilson, K. F.
Show abstract
The ability of cancer cells to survive microenvironmental stresses is critical for tumor progression and metastasis; however, how they survive these challenges is not fully understood. Here, we describe a novel multiprotein complex (DockTOR) essential for the survival of cancer cells under stress, triggered by the GTPase Cdc42 and a signaling partner Dock7, which includes AKT, mTOR, and the mTOR regulators TSC1, TSC2, and Rheb. DockTOR enables cancer cells to maintain a low but critical mTORC2-dependent phosphorylation of AKT during serum deprivation by preventing AKT dephosphorylation through an interaction between phospho-AKT and the Dock7 DHR1 domain. This activity stimulates a Raptor-independent but Rapamycin-sensitive mTOR/S6K activity necessary for survival. These findings address long-standing questions of how Cdc42 signals result in mTOR activation and demonstrate how cancer cells survive conditions when growth factor-dependent activation of mTORC1 is off. Determining how cancer cells survive stress conditions could identify vulnerabilities that lead to new therapeutic strategies.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- HUWE1 stimulates mTORC1 activity by enhancing Rheb interaction with mTORC1 and supports de novo pyrimidine synthesis 96%
- An Aurora kinase A-BOD1L1-PP2A B56 Axis promotes chromosome segregation fidelity 95%
- mTORC1 activity oscillates throughout the cell cycle promoting mitotic entry and differentially influencing autophagy induction 95%
Similar papers in this journal
- RAF inhibitors activate the integrated stress response by direct activation of GCN2 95%
- Cancer-Associated USP28 Missense Mutations Disrupt 53BP1 Interaction and p53 Stabilization 94%
- CDK4 inactivation balances resistance to apoptosis with heightened metabolic sensitivity in triple negative breast cancer cells 94%
Similar papers in this journal
- Inhibition of the YAP-MMB interaction and targeting NEK2 as potential therapeutic strategies for YAP-driven cancers 94%
- Oncogenic RAS sensitizes cells to drug-induced replication stress via transcriptional silencing of P53 94%
- Proteasome Regulation by Reversible Tyrosine Phosphorylation at the Membrane 94%
Similar papers in this journal
- Protein proximity networks and functional evaluation of the Casein Kinase 1 γ family reveals unique roles for CK1γ3 in WNT signaling 95%
- Stablization of Interdomain Interactions in G protein αi Subunits Determines Gαi Subtype Signaling Specificity 94%
- Targeting the Protein-Protein Interaction Between the CDC37 Co-Chaperone and Client Kinases by an Allosteric RAF Dimer Breaker 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.