PXD054670

PXD054670 is an original dataset announced via ProteomeXchange.

Title	A Polyamine-mediated Posttranslational Modification Required For Macrophage Tissue Residency – Differential proteome analysis of DHPS deficient macrophages
Description	Tissue resident macrophages (MTRs) regulate tissue repair and homeostasis by clearing cell debris, and are thought to form the first line of defense against pathogens. MTRs form early in life and self-renew locally. However, during tissue damage or disease, bone-marrow derived monocytes enter tissue sites and differentiate into MTRs, repairing the tissue and replenishing macrophages in the niche. How MTR versus monocyte-derived macrophages recruited during inflammation contribute to health and disease, and the cell-intrinsic mechanisms that control the monocyte to MTR transition across tissues, remain elusive. Here we show that deoxyhypusine synthase (DHPS), an enzyme that mediates the spermidine-dependent hypusine modification of the translation factor eIF5A, is required for the differentiation and maintenance of MTR. EIF5A is the only protein to contain hypusine, and the only function of DHPS (together with DOHH) is to hypusinate eIF5A. Hypusinated-eIF5A enhances the translation efficiency of certain mRNA transcripts that lead to ribosome stalling, including those with polyproline motifs. MTRs in tissues of young mice with myelomonocytic cell deletions in DHPS (Dhps-M mice; hypusination deficient eIF5A) had abnormal expression of macrophage tissue resident markers, and MTRs themselves declined with age. Single cell transcriptional analysis of DHPS-deficient peritoneal macrophages indicated a block in the transition from monocyte to mature MTRs, while proteomics revealed decreased expression of cell adhesion and signaling molecules. Notably, sequencing of ribosome-engaged transcripts suggested that certain cell adhesion and signaling molecules are hyper-dependent on hypusinated eIF5A for efficient translation.
HostingRepository	PRIDE
AnnounceDate	2026-03-23
AnnouncementXML	Submission_2026-03-22_20:37:05.447.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gerhard Mittler
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; deamidated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-07 04:42:50	ID requested
⏵ 1	2026-03-22 20:37:06	announced

Carrizo GE, Lin P, Lee SH, Shenderov K, Bl, é, riot C, Cha M, Schimmelpfennig L, Shen Z, van Teijlingen Bakker N, Grzes KM, Kelly B, Safinia N, Schole KL, Musa Y, Mittler G, Zen Y, Pearce EJ, Ginhoux F, Sanin DE, Puleston DJ, Pearce EL, The transition from monocyte to tissue-resident macrophage requires DHPS. Nature, 651(8106):763-774(2026) [pubmed]

10.1038/s41586-025-09972-2;

submitter keyword: eIF5A, DIA, Spectronaut, DDA spectral library, tissue resident macrophage proteomics, MaxQuant, label-free quantification, deoxyhypusine synthase (DHPS),Hypusine

Gerhard Mittler
contact affiliation	Max Planck Institute of Immunobiology and Epigenetics Proteomics Unit Stuebeweg 51 79108 Freiburg, Germany
contact email	mittler@ie-freiburg.mpg.de
lab head
Gerhard Mittler
contact affiliation	Proteomics Unit, Max Planck Institute of Immunobiology and Epigenetics
contact email	mittler@ie-freiburg.mpg.de
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/2026/03/PXD054670

PRIDE project URI

• PRIDE
  1. PXD054670
     1. Label: PRIDE project
     2. Name: A Polyamine-mediated Posttranslational Modification Required For Macrophage Tissue Residency – Differential proteome analysis of DHPS deficient macrophages