PXD018896

PXD018896 is an original dataset announced via ProteomeXchange.

Title	A broad response to intracellular long-chain polyphosphate in human cells
Description	Polyphosphates (PolyP) are highly anionic, linear polymers composed of long chains of inorganic phosphates linked together by phosphoanhydride bonds. PolyP chains are found in all kingdoms of life, and play roles in phosphate homeostasis, cell growth, infection, and blood coagulation. Unlike in bacteria and yeast, the mammalian enzymes responsible for the synthesis and degradation of polyP are unknown, which presents a challenge for the study of polyP in higher eukaryotes. To overcome this, we use a system to produce polyP inside of human cells through the ectopic expression of the E. coli Ppk1 synthetic enzyme. Here, we present the results from large-scale transcriptomic and proteomic analyses of polyP producing HEK293T cells. We uncovered >350 RNAs and 14 proteins that show changes following in vivo polyP accumulation. Follow up on specific hits revealed that the internal accumulation of polyP resulted in a significant decrease in the dehydrogenase/reductase DHRS2 without a corresponding increase in p53 phosphorylation, and activation of the ERK1/2-ERG1 signaling axis. Finally, following upregulation of internal polyP we observed the relocalization and redistribution of several nuclear proteins, including chromatin bound proteins DEK, TAF10, GTF2I and the translation initiation factor eIF5b. Altogether, our work serves as a novel resource to understand the impact of increased intracellular polyP in mammalian cells.
HostingRepository	PRIDE
AnnounceDate	2020-09-24
AnnouncementXML	Submission_2020-09-23_22:22:09.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD018896
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Mathieu Lavallée-Adam
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Ammonia-loss; Phospho; Deamidated; Dehydrated; Oxidation; Dioxidation; Acetyl; monohydroxylated residue; acetylated residue; Carbamidomethyl; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-29 04:09:25	ID requested
⏵ 1	2020-09-23 22:22:09	announced

Dataset with its publication pending

submitter keyword: Human, HEK293T, LC-MS/MS

Michael Downey
contact affiliation	Department of Cellular and Molecular Medicine and Ottawa Institute of Systems Biology, University of Ottawa, Canada
contact email	mdowne2@uottawa.ca
lab head
Mathieu Lavallée-Adam
contact affiliation	University of Ottawa
contact email	mathieu.lavallee@uottawa.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018896
     1. Label: PRIDE project
     2. Name: A broad response to intracellular long-chain polyphosphate in human cells