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PXD007212-1

PXD007212 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleInhibition of nuclear PTEN tyrosine phosphorylation enhances glioma radiation sensitivity through attenuated DNA repair
DescriptionGlioblastoma (GBM) is the most lethal brain tumour that occurs in adults and treatment for GBM has been largely unsuccessful. Ionizing radiation (IR) and chemotherapeutic agents are employed as standard of care treatment for GBM patients and both result in DNA damage. Previous data identified phosphorylation of PTEN at tyrosine 240 (pY240) in samples from patients with recurrent GBM receiving standard of care treatment and was associated with decreased overall survival. Here we demonstrate that pY240 PTEN that was triggered by FGFR2 signaling, enhanced DNA repair by facilitating the loading of PTEN onto chromatin through its interaction with KI-67 and subsequent recruitment of the DNA repair protein, RAD51, to sites of DNA damage. Thus, tumour cells with pY240 PTEN are efficient at repairing DNA damage which would be predicted to result in resistance to therapy. These findings suggest the FGFR-pY240 PTEN-DNA repair mechanism as a therapeutic target for enhancing GBM therapy.
HostingRepositoryMassIVE
AnnounceDate2019-04-15
AnnouncementXMLSubmission_2019-04-15_16:01:00.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterclaudio
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListLabel:13C(6)15N(4); Label:13C(6)15N(2); Carboxymethyl
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-08-07 14:58:25ID requested
12019-04-15 16:01:02announced
Publication List
Ma J, Benitez JA, Li J, Miki S, Ponte de Albuquerque C, Galatro T, Orellana L, Zanca C, Reed R, Boyer A, Koga T, Varki NM, Fenton TR, Nagahashi Marie SK, Lindahl E, Gahman TC, Shiau AK, Zhou H, DeGroot J, Sulman EP, Cavenee WK, Kolodner RD, Chen CC, Furnari FB, Inhibition of Nuclear PTEN Tyrosine Phosphorylation Enhances Glioma Radiation Sensitivity through Attenuated DNA Repair. Cancer Cell, 35(3):504-518.e7(2019) [pubmed]
Keyword List
submitter keyword: Glioblastoma, DNA Repair, PTEN
Contact List
Frank B. Furnari1
contact affiliationLudwig Institute for Cancer Research, San Diego branch
contact emailffurnari@ucsd.edu
lab head
claudio
contact affiliationLICR, UCSD
contact emailcpontede@gmail.com
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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