PXD006461

PXD006461 is an original dataset announced via ProteomeXchange.

Title	mTORC2 regulates amino acid metabolism in cancer by phosphorylation of the cystine-glutamate antiporter xCT
Description	Mutations in cancer reprogram amino acid metabolism to drive tumor growth, but the molecular mechanisms are not well understood. Using an unbiased proteomic screen, we identified mTORC2 as a critical regulator of amino acid metabolism in cancer via phosphorylation of the cystine-glutamate antiporter xCT. mTORC2 phosphorylates serine 26 at the cytosolic N-terminus of xCT, inhibiting its activity. Genetic inhibition of mTORC2, or pharmacologic mTOR kinase inhibition, promotes glutamate secretion, cystine uptake and incorporation into glutathione linking growth factor receptor signaling with amino acid uptake and utilization. These results identify an unanticipated mechanism of amino acid metabolic reprogramming in cancer, enabling tumor cells to adapt to changing environmental conditions.
HostingRepository	PRIDE
AnnounceDate	2017-06-28
AnnouncementXML	Submission_2017-06-27_23:38:19.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Claudio Ponte de Albuquerque
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C: 4x(15)N labeled L-arginine; 6x(13)C: 2x(15)N labeled L-lysine; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2017-05-08 01:35:01	ID requested
⏵ 1	2017-06-27 23:38:21	announced

Gu Y, Albuquerque CP, Braas D, Zhang W, Villa GR, Bi J, Ikegami S, Masui K, Gini B, Yang H, Gahman TC, Shiau AK, Cloughesy TF, Christofk HR, Zhou H, Guan KL, Mischel PS, mTORC2 Regulates Amino Acid Metabolism in Cancer by Phosphorylation of the Cystine-Glutamate Antiporter xCT. Mol Cell, 67(1):128-138.e7(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: xCT, mTORC2

Paul S. Mischel3
contact affiliation	Ludwig Institute for Cancer Research, University of California San Diego, CA. Moores Cancer Center, UCSD School of Medicine, La Jolla, CA. Department of Pathology, UCSD School of Medicine, La Jolla, CA
contact email	pmischel@ucsd.edu
lab head
Claudio Ponte de Albuquerque
contact affiliation	UCSD
contact email	cpontede@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/06/PXD006461

PRIDE project URI

• PRIDE
  1. PXD006461
     1. Label: PRIDE project
     2. Name: mTORC2 regulates amino acid metabolism in cancer by phosphorylation of the cystine-glutamate antiporter xCT