PXD034117-1

PXD034117 is an original dataset announced via ProteomeXchange.

Title	Dual roles of mTORC1-dependent activation of the ubiquitin-proteasome system in muscle proteostasis
Description	Muscle size is controlled by the PI3K-PKB/Akt-mTORC1-FoxO pathway, which integrates signals from growth factors, energy and amino acids to activate protein synthesis and inhibit protein breakdown. While mTORC1 activity is necessary for PKB/Akt-induced muscle hypertrophy, its constant activation alone induces muscle atrophy. Here we show that this paradox is based on mTORC1 activity promoting protein breakdown through the ubiquitin-proteasome system (UPS) by simultaneously inducing ubiquitin E3 ligase expression via feedback inhibition of PKB/Akt and proteasome biogenesis via Nuclear Factor Erythroid 2-Like 1 (Nrf1). Muscle growth was restored by reactivation of PKB/Akt, but not by Nrf1 knockdown, implicating ubiquitination as the limiting step. However, both PKB/Akt activation and proteasome depletion by Nrf1 knockdown led to an immediate disruption of proteome integrity with rapid accumulation of damaged material. These data highlight the physiological importance of mTORC1-mediated PKB/Akt inhibition and point to juxtaposed roles of the UPS in atrophy and proteome integrity.
HostingRepository	PRIDE
AnnounceDate	2022-10-28
AnnouncementXML	Submission_2022-10-28_05:55:10.634.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD034117
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	AlexanderSchmidt
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-25 06:53:30	ID requested
⏵ 1	2022-10-28 05:55:10	announced
2	2023-11-14 08:56:32	announced	2023-11-14: Updated project metadata.

10.6019/PXD034117;

submitter keyword: TMT, LC-MS,mTOR, muscle

AlexanderSchmidt
contact affiliation	Proteomics Core Facility, Biozentrum, University of Basel, Switzerland
contact email	alex.schmidt@unibas.ch
lab head
AlexanderSchmidt
contact affiliation	Proteomics Core Facility
contact email	alex.schmidt@unibas.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034117
     1. Label: PRIDE project
     2. Name: Dual roles of mTORC1-dependent activation of the ubiquitin-proteasome system in muscle proteostasis