PXD006209 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:02:04.548.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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2017-03-30 01:13:53 | ID requested | |
1 | 2018-10-08 04:11:04 | announced | |
⏵ 2 | 2024-10-22 04:02:09 | announced | 2024-10-22: Updated project metadata. |
Publication List
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] |
10.1038/leu.2017.160; |
Keyword List
curator keyword: Biomedical |
submitter keyword: PTEN, T-ALL, HIF,T cells |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD006209
- Label: PRIDE project
- Name: Control of amino-acid transport coordinates metabolic reprogramming in T cell malignancy