PXD006209

PXD006209 is an original dataset announced via ProteomeXchange.

Title	Control of amino-acid transport coordinates metabolic reprogramming in T cell malignancy
Description	Analysis of murine model of T cell acute lymphoblastic leukemia (T-ALL) caused by deletion of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) reveals that primary T-ALL cells have high transport rates for multiple nutrients. In particular, high levels of leucine transport in T-ALL fuels mammalian target of rapamycin complex 1 (mTORC1) activity which then sustains expression of hypoxia inducible factor-1a (HIF1a) and c-Myc, the drivers of glucose transport. A key finding is that PTEN deletion and phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) accumulation is insufficient to initiate leucine uptake, mTORC1 activity, HIF1a or c-Myc expression in T cells and hence cannot drive T-ALL metabolic reprogramming. Instead, a key regulator for leucine transport in T-ALL is identified as NOTCH. Mass spectrometry based proteomics identifies SLC7A5 as the dominant System L-amino acid transporter in primary PTEN-/- T-ALL cells. Importantly, expression of SLC7A5 is critical for the malignant transformation induced by PTEN deletion. These data highlight the importance of regulated amino acid transport for T cell malignancies and how a single amino acid transporter can play a key role.
HostingRepository	PRIDE
AnnounceDate	2018-10-08
AnnouncementXML	Submission_2018-10-08_04:11:03.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jens Hukelmann
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	carbamoylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-03-30 01:13:53	ID requested
⏵ 1	2018-10-08 04:11:04	announced

Grzes KM, Swamy M, Hukelmann JL, Emslie E, Sinclair LV, Cantrell DA, Control of amino acid transport coordinates metabolic reprogramming in T-cell malignancy. Leukemia, 31(12):2771-2779(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: T cells, PTEN, HIF, T-ALL

Doreen Ann Cantrell
contact affiliation	Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, UK
contact email	d.a.cantrell@dundee.ac.uk
lab head
Jens Hukelmann
contact affiliation	University of Dundee
contact email	jhukelmann@dundee.ac.uk
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/2018/10/PXD006209

PRIDE project URI

• PRIDE
  1. PXD006209
     1. Label: PRIDE project
     2. Name: Control of amino-acid transport coordinates metabolic reprogramming in T cell malignancy