TY  - JOUR
A1  - Klann, Kevin
A1  - Tascher, Georg
A1  - Münch, Christian
T1  - Functional translatome proteomics reveal converging and dose-dependent regulation by mtorc1 and eif2α
T2  - Molecular cell
N2  - Regulation of translation is essential during stress. However, the precise sets of proteins regulated by the key translational stress responses—the integrated stress response (ISR) and mTORC1—remain elusive. We developed multiplexed enhanced protein dynamics (mePROD) proteomics, adding signal amplification to dynamic-SILAC and multiplexing, to enable measuring acute changes in protein synthesis. Treating cells with ISR/mTORC1-modulating stressors, we showed extensive translatome modulation with ∼20% of proteins synthesized at highly reduced rates. Comparing translation-deficient sub-proteomes revealed an extensive overlap demonstrating that target specificity is achieved on protein level and not by pathway activation. Titrating cap-dependent translation inhibition confirmed that synthesis of individual proteins is controlled by intrinsic properties responding to global translation attenuation. This study reports a highly sensitive method to measure relative translation at the nascent chain level and provides insight into how the ISR and mTORC1, two key cellular pathways, regulate the translatome to guide cellular survival upon stress.
KW  - proteomics
KW  - integrated stress response
KW  - translation
KW  - stress response
KW  - mTOR
KW  - unfolded protein response
KW  - cap-dependent translation
KW  - SILAC
KW  - TMT
KW  - pulse labeling
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53068
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-530682
SN  - 1097-4164
SN  - 1097-2765
N1  - This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
VL  - 77
IS  - 4
SP  - 913
EP  - 925.e4
PB  - Cell Press ; Elsevier
CY  - [Cambridge, Mass.] ; New York, NY
ER  -