Dataset Information

Fine-tuning nucleophosmin in macrophage differentiation and activation.

ABSTRACT: M-CSF-driven differentiation of peripheral blood monocytes is one of the sources of tissue macrophages. In humans and mice, the differentiation process involves the activation of caspases that cleave a limited number of proteins. One of these proteins is nucleophosmin (NPM1), a multifunctional and ubiquitous protein. Here, we show that caspases activated in monocytes exposed to M-CSF cleave NPM1 at D213 to generate a 30-kDa N-terminal fragment. The protein is further cleaved into a 20-kDa fragment, which involves cathepsin B. NPM1 fragments contribute to the limited motility, migration, and phagocytosis capabilities of resting macrophages. Their activation with lipopolysaccharides inhibits proteolytic processes and restores expression of the full-length protein that negatively regulates the transcription of genes encoding inflammatory cytokines (eg, NPM1 is recruited with NF-?B on the MCP1 gene promoter to decrease its transcription). In mice with heterozygous npm gene deletion, cytokine production in response to lipopolysaccharides, including CXCL1 (KC), MCP1, and MIP2, is dramatically enhanced. These results indicate a dual function of NPM1 in M-CSF-differentiated macrophages. Proteolysis of the protein participates in the establishment of a mature macrophage phenotype. In response to inflammatory stimuli, the full-length protein negatively regulates inflammatory cytokine production.

SUBMITTER: Guery L

PROVIDER: S-EPMC3208284 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fine-tuning nucleophosmin in macrophage differentiation and activation.

Guery Leslie L Benikhlef Naïma N Gautier Thomas T Paul Catherine C Jego Gaetan G Dufour Erick E Jacquel Arnaud A Cally Radj R Manoury Bénédicte B Vanden Berghe Tom T Vandenabeele Peter P Droin Nathalie N Solary Eric E

Blood 20110829 17

M-CSF-driven differentiation of peripheral blood monocytes is one of the sources of tissue macrophages. In humans and mice, the differentiation process involves the activation of caspases that cleave a limited number of proteins. One of these proteins is nucleophosmin (NPM1), a multifunctional and ubiquitous protein. Here, we show that caspases activated in monocytes exposed to M-CSF cleave NPM1 at D213 to generate a 30-kDa N-terminal fragment. The protein is further cleaved into a 20-kDa fragme ...[more]

PMID: 21876121

Similar Datasets

Project description:To create a dataset of PSMs that does not exhibit tryptic bias, we selected PSMs with a uniform distribution of amino acids at the C-terminal peptide positions from two datasets: MassIVE-KB [Wang2018] and PROSPECT [Shouman2022]. The MassIVE-KB dataset contains 30 million PSMs and consists entirely of data generated using trypsin; hence, only a small proportion of the MassIVE-KB peptides do not end in K or R, corresponding to those that appear at the C-terminus of the corresponding protein. The PROSPECT dataset is a collection of 61 million PSMs generated from synthetic peptides. To avoid overrepresentation of some peptides in this dataset, we randomly selected at most 100 PSMs per unique peptide, similar to the processing that was done during the creation of the MassIVE-KB dataset. This pre-selection step reduced the size of the PROSPECT dataset to 12.6 million PSMs. Finally, to create a non-enzymatic dataset containing 1 million peptides, we selected 50,000 PSMs for each canonical amino acid. These PSMs were selected at random from MassIVE-KB, then supplemented as necessary from PROSPECT to obtain the desired count (see Yilmaz et al. [Yilmaz2023] Supplementary Table S1). This dataset contained PSMs from 247,859 unique peptides, which were randomly split into training, validation and test sets in the ratio 80/10/10. FTP directory contains the mgf files corresponding to train, validation and test splits. [Wang2018] M. Wang, J. Wang, J. Carver, B. Pullman, S. Won Cha, N. Bandeira, "Assembling the Community-Scale Discoverable Human Proteome", Cell Systems, Volume 7, Issue 4, 2018. [Shouman2022] O. Shouman, W. Gabriel, V. Giurcoiu, V. Sternlicht, M. Wilhelm, "PROSPECT: Labeled Tandem Mass Spectrometry Dataset for Machine Learning in Proteomics", NeurIPS Datasets and Benchmarks, 2022 [Yilmaz2023] M. Yilmaz*, W. Fondrie*, W. Bittremieux, R. Nelson, V. Ananth, S. Oh, and W. Noble,"Sequence-to-sequence translation from mass spectra to peptides with a transformer model", bioRxiv, 2023

Dataset Information

Fine-tuning nucleophosmin in macrophage differentiation and activation.

Publications

Fine-tuning nucleophosmin in macrophage differentiation and activation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets