PXD034517-1

PXD034517 is an original dataset announced via ProteomeXchange.

Title	MYC sensitises cells to apoptosis by driving energetic demand
Description	The MYC oncogene is a potent driver of growth and proliferation but also sensitises cells to apoptosis, which limits its oncogenic potential. MYC induces several biosynthetic programmes and primary cells overexpressing MYC are highly sensitive to glutamine withdrawal suggesting that MYC-induced sensitisation to apoptosis may be due to an imbalance of metabolic/energetic supply and demand. Here we show that MYC elevates global transcription and translation, even in the absence of glutamine, revealing metabolic demand without corresponding supply. Glutamine withdrawal from MRC-5 fibroblasts depleted key TCA cycle metabolites and, in combination with MYC activation, led to AMP accumulation and nucleotide catabolism indicative of energetic stress. Further analyses revealed that glutamine supports viability through TCA cycle energetics rather than asparagine biosynthesis and that TCA cycle inhibition confers tumour suppression on MYC- driven lymphoma in vivo. In summary, glutamine supports the viability of MYC- overexpressing cells through an energetic rather than a biosynthetic mechanism.
HostingRepository	PRIDE
AnnounceDate	2022-08-11
AnnouncementXML	Submission_2022-08-11_11:58:12.317.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jimi Wills
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-14 09:40:37	ID requested
⏵ 1	2022-08-11 11:58:12	announced
2	2023-11-14 08:57:08	announced	2023-11-14: Updated project metadata.

10.1038/S41467-022-32368-Z;

submitter keyword: MYC, apoptosis, glutamine, energy, adenylate kinase, nucleotide catabolism, nucleotide biosynthesis, pentose phosphate pathway, metabolic flux

Andrew J Finch
contact affiliation	Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London, UK
contact email	a.finch@qmul.ac.uk
lab head
Jimi Wills
contact affiliation	Firefinch Software Ltd formerly Univeristy of Edinburgh
contact email	jimi@firefinch.io
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/08/PXD034517

PRIDE project URI

• PRIDE
  1. PXD034517
     1. Label: PRIDE project
     2. Name: MYC sensitises cells to apoptosis by driving energetic demand