MNK Controls mTORC1:Substrate Association through Regulation of TELO2 Binding with mTORC1.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Brown, MC; Gromeier, M

Published Date

  • February 7, 2017

Published In

Volume / Issue

  • 18 / 6

Start / End Page

  • 1444 - 1457

PubMed ID

  • 28178522

Pubmed Central ID

  • 28178522

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2017.01.023

Language

  • eng

Conference Location

  • United States