PXD054314-1

PXD054314 is an original dataset announced via ProteomeXchange.

Title	The proto-oncogene tyrosine kinase c-SRC facilitates glioblastoma progression by remodeling fatty acid synthesis
Description	Increased 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.
HostingRepository	PRIDE
AnnounceDate	2024-07-29
AnnouncementXML	Submission_2024-07-28_21:09:26.560.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wentao Zhao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-28 20:36:09	ID requested
⏵ 1	2024-07-28 21:09:26	announced

Dataset with its publication pending

submitter keyword: ACSS2, Fatty acid synthesis, ACLY

Wentao Zhao
contact affiliation	the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University
contact email	zhaowentao@xmu.edu.cn
lab head
Wentao Zhao
contact affiliation	Xiamen University
contact email	771526995@qq.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054314
     1. Label: PRIDE project
     2. Name: The proto-oncogene tyrosine kinase c-SRC facilitates glioblastoma progression by remodeling fatty acid synthesis