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PXD054314

PXD054314 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe proto-oncogene tyrosine kinase c-SRC facilitates glioblastoma progression by remodeling fatty acid synthesis
DescriptionIncreased fatty acid synthesis benefits glioblastoma malignancy. However, the coordinated regulation of cytosolic acetyl-CoA production, the exclusive substrate for fatty acid synthesis, remains unclear. Here, we show that proto-oncogene tyrosine kinase c-SRC is activated in glioblastoma and remodels cytosolic acetyl-CoA production for fatty acid synthesis. Firstly, acetate is an important substrate for fatty acid synthesis in glioblastoma. c-SRC phosphorylates acetyl-CoA synthetase ACSS2 at Tyr530 and Tyr562 to stimulate the conversion of acetate to acetyl-CoA in cytosol. Secondly, c-SRC inhibits citrate-derived acetyl-CoA synthesis by phosphorylating ATP-citrate lyase ACLY at Tyr682. ACLY phosphorylation shunts citrate to IDH1-catalyzed NADPH production to provide reducing equivalent for fatty acid synthesis. The c-SRC-unresponsive double-mutation of ACSS2 and ACLY significantly reduces fatty acid synthesis and hampers glioblastoma progression. In conclusion, this remodeling fulfills the dual needs of glioblastoma cells for both acetyl-CoA and NADPH in fatty acid synthesis and provides evidence for glioma treatment by c-SRC inhibition.
HostingRepositoryPRIDE
AnnounceDate2024-07-29
AnnouncementXMLSubmission_2024-07-28_21:09:26.560.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterWentao Zhao
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentTripleTOF 5600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-07-28 20:36:09ID requested
12024-07-28 21:09:26announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: ACSS2, Fatty acid synthesis, ACLY
Contact List
Wentao Zhao
contact affiliationthe First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University
contact emailzhaowentao@xmu.edu.cn
lab head
Wentao Zhao
contact affiliationXiamen University
contact email771526995@qq.com
dataset submitter
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Dataset FTP location
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