| Fine-tuning nucleophosmin in macrophage differentiation and activation. | |
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MedLine Citation:
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PMID: 21876121 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 lipopolysacchararides (LPS) inhibits the proteolytic processes and restores the expression of the full-length protein that negatively regulates the transcription of genes encoding inflammatory cytokines, e.g. NPM1 is recruited with NF-κB on MCP1 gene promoter to decrease its transcription. In mice with heterozygous npm gene deletion, cytokine production in response to LPS, 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. |
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Authors:
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Leslie Guery; Naïma Benikhlef; Thomas Gautier; Catherine Paul; Gaetan Jego; Erick Dufour; Arnaud Jacquel; Radj Cally; Bénédicte Manoury; Tom Vanden Berghe; Peter Vandenabeele; Nathalie Droin; Eric Solary |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-29 |
Journal Detail:
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Title: Blood Volume: - ISSN: 1528-0020 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Inserm UMR866, Faculte de Medecine, Dijon, France; |
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Descriptor/Qualifier:
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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