PXD019347

PXD019347 is an original dataset announced via ProteomeXchange.

Title	Formate-induced phospho-signalling
Description	The mitochondrial serine catabolism to formate induces a metabolic switch to a hypermetabolic state with high rates of glycolysis, purine synthesis and pyrimidine synthesis. While formate is a purine precursor it is not obvious link between formate and pyrimidine synthesis. Methods Here we combine phospho-proteome and metabolic profiling to determine how formate induces pyrimidine synthesis. We discover that formate induces CAD phosphorylation. Mechanistically formate induces mTORC1 activity as quantified by S6K1 phosphorylation, which is known to phosphorylate CAD and increase its enzymatic activity. Treatment with the allosteric mTORC1 inhibitor rapamycin abrogates CAD phosphorylation and pyrimidine synthesis induced by formate. We conclude that formate activates mTORC1 and induces pyrimidine synthesis via increasing CAD activity.
HostingRepository	PRIDE
AnnounceDate	2020-09-28
AnnouncementXML	Submission_2020-09-27_23:36:06.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sara Zanivan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-22 03:32:28	ID requested
⏵ 1	2020-09-27 23:36:07	announced

Tait-Mulder J, Hodge K, Sumpton D, Zanivan S, Vazquez A, The conversion of formate into purines stimulates mTORC1 leading to CAD-dependent activation of pyrimidine synthesis. Cancer Metab, 8():20(2020) [pubmed]

submitter keyword: Phosphoproteomics, MS, Formate, Metabolism, Cancer

Sara Zanivan
contact affiliation	CRUK Beatson Institute
contact email	s.zanivan@beatson.gla.ac.uk
lab head
Sara Zanivan
contact affiliation	Tumour Microenvironment & Proteomics
contact email	s.zanivan@beatson.gla.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019347
     1. Label: PRIDE project
     2. Name: Formate-induced phospho-signalling