PXD002724

PXD002724 is an original dataset announced via ProteomeXchange.

Title	Analysis of proteins that rapidly change upon mTORC1 repression identifies Park7 as a novel protein aberrantly expressed in Tuberous Sclerosis Complex
Description	Many biological processes involve the mechanistic/mammalian target of rapamycin complex 1 (mTORC1). Thus, the challenge of deciphering mTORC1-mediated functions during normal and pathological states in the central nervous system is steep. Because mTORC1 is at the core of translation, we have investigated mTORC1 function in global and regional protein expression. Activation of mTORC1 has been generally regarded to promote translation. Few but recent works have demonstrated that suppression of mTORC1 can promote local protein synthesis. Moreover, excessive mTORC1 activation during disease states represses basal and activity-induced protein synthesis. To determine the role of mTORC1 activation in protein expression, we have used an unbiased, large scale proteomic approach. We provide evidence that a brief repression of mTORC1 activity in vivo by rapamycin has little affect globally, yet leads to a significant remodeling of synaptic proteins, in particular those proteins that reside in the postsynaptic density (PSD). We have also found that curtailing the activity of mTORC1 bidirectionally alters the expression of proteins associated with epilepsy, Alzheimer’s disease, and autism spectrum disorder (ASD)—neurological disorders that exhibit elevated mTORC1 activity. Through a protein-protein interaction network analysis, we have identified common proteins shared among these mTOR-related diseases. One such protein is Parkinson protein 7 (PARK7) which has been implicated in Parkinson’s disease, yet not associated with epilepsy, AD, or ASD. To verify our finding, we provide evidence that the protein expression of PARK7, including new protein synthesis, is sensitive to mTORC1 inhibition. Using cultured neurons from a mouse model of tuberous sclerosis complex (TSC), a disease that displays both epilepsy and ASD phenotypes and has overactive mTOR signaling, we show that PARK7 protein is elevated in the dendrites. Our work offers a comprehensive view of mTORC1 and its role in regulating regional protein expression in normal and diseased states.
HostingRepository	PRIDE
AnnounceDate	2016-02-19
AnnouncementXML	Submission_2016-02-19_05:48:04.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rui Zhu
SpeciesList	scientific name: Rattus rattus (Black rat); NCBI TaxID: 10117;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2015-08-14 01:43:05	ID requested
⏵ 1	2016-02-19 05:48:05	announced

Niere F, Namjoshi S, Song E, Dilly GA, Schoenhard G, Zemelman BV, Mechref Y, Raab-Graham KF, Analysis of Proteins That Rapidly Change Upon Mechanistic/Mammalian Target of Rapamycin Complex 1 (mTORC1) Repression Identifies Parkinson Protein 7 (PARK7) as a Novel Protein Aberrantly Expressed in Tuberous Sclerosis Complex (TSC). Mol Cell Proteomics, 15(2):426-44(2016) [pubmed]

curator keyword: Biomedical, Biological

submitter keyword: LC-MS

Yehia Mechref
contact affiliation	Texas Tech University
contact email	yehia.mechref@ttu.eud
lab head
Rui Zhu
contact affiliation	Texas Tech University
contact email	rui.zhu@ttu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002724
     1. Label: PRIDE project
     2. Name: Analysis of proteins that rapidly change upon mTORC1 repression identifies Park7 as a novel protein aberrantly expressed in Tuberous Sclerosis Complex