| First Author | Brown MC | Year | 2017 |
| Journal | Cell Rep | Volume | 18 |
| Issue | 6 | Pages | 1444-1457 |
| PubMed ID | 28178522 | Mgi Jnum | J:254036 |
| Mgi Id | MGI:6103735 | Doi | 10.1016/j.celrep.2017.01.023 |
| Citation | Brown MC, et al. (2017) MNK Controls mTORC1:Substrate Association through Regulation of TELO2 Binding with mTORC1. Cell Rep 18(6):1444-1457 |
| abstractText | The mechanistic target of rapamycin (mTOR) integrates numerous stimuli and coordinates the adaptive response of many cellular processes. To accomplish this, mTOR associates with distinct co-factors that determine its signaling output. While many of these co-factors are known, in many cases their function and regulation remain opaque. The MAPK-interacting kinase (MNK) contributes to rapamycin resistance in cancer cells. Here, we demonstrate that MNK sustains mTORC1 activity following rapamycin treatment and contributes to mTORC1 signaling following T cell activation and growth stimuli in cancer cells. We determine that MNK engages with mTORC1, promotes mTORC1 association with the phosphatidyl inositol 3'' kinase-related kinase (PIKK) stabilizer, TELO2, and facilitates mTORC1:substrate binding. Moreover, our data suggest that DEPTOR, the endogenous inhibitor of mTOR, opposes mTORC1:substrate association by preventing TELO2:mTORC1 binding. Thus, MNK orchestrates counterbalancing forces that regulate mTORC1 enzymatic activity. |
