PXD017474

PXD017474 is an original dataset announced via ProteomeXchange.

Title	PCNA has specific functions in regulation of metabolism in haematological cells
Description	PCNA´s essential roles in DNA replication and repair are well established, while it’s recently discovered non-canonical roles in cellular signalling and regulation of metabolism are less explored. Recent data has indicated that PCNA has a specific non-canonical role in cells of haematological origin. In the present study we have explored this further at the system level by extensive protein-, gene expression, and metabolite profiling combined with integrated pathway analysis and by 13C label experimentation, Here we show that impairing PCNA´s scaffold functions led to massive changes in cellular signalling, but more importantly, a strong reduction in glycolytic metabolites and nucleoside phosphate pools in haematological cancer cell lines was detected, including multiple myeloma cells and acute myelogen leukaemia cells. This was not observed in cell lines from solid tissues such as kidney, bladder and prostate, nor in primary monocytes. Lipopolysaccharide (LPS) stimulated monocytes on the other hand, responded to treatment similarly to the haematological cancer cells, suggesting that cellular stress is an important factor for the response to the APIM-peptide in haematological cells. Integrated Pathway analysis of the metabolite and protein datasets revealed that protein ubiquitination and antigen presentation pathways are affected in haematopoietic cancer cells upon treatment. Focusing on one multiple myeloma cell line we further verified these trends by gene-expression and show that the consequences of reduced central carbon metabolite pools and energy charge is impaired redox and HIF1A regulation. Altogether, our data suggests that PCNA has an important role in regulation of cytoplasmic stress via regulation of central carbon metabolism in haematological cells that can be targeted in cancer treatment.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:24:31.835.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Animesh Sharma
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-12 03:02:29	ID requested
1	2023-03-10 13:37:14	announced
⏵ 2	2023-11-14 08:24:32	announced	2023-11-14: Updated project metadata.

R, ø, st LM, R, æ, der SB, Olaisen C, S, ø, gaard CK, Sharma A, Bruheim P, Otterlei M, PCNA regulates primary metabolism by scaffolding metabolic enzymes. Oncogene, 42(8):613-624(2023) [pubmed]

submitter keyword: PI3K/AKT pathway, metabolomics, systems-level study, signalome, cell signalling, redox metabolism,APIM, central carbon metabolism, kinome

Marit Otterlei
contact affiliation	Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), PO Box 8905, N-7491, Trondheim, Norway Phone: +47 72573075, Fax: +47 72576400
contact email	marit.otterlei@ntnu.no
lab head
Animesh Sharma
contact affiliation	Engineer at NTNU, Norway
contact email	sharma.animesh@gmail.com
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/2023/03/PXD017474

PRIDE project URI

• PRIDE
  1. PXD017474
     1. Label: PRIDE project
     2. Name: PCNA has specific functions in regulation of metabolism in haematological cells