Journal
IMMUNOLOGICAL REVIEWS
Volume 273, Issue 1, Pages 344-356Publisher
WILEY
DOI: 10.1111/imr.12449
Keywords
apoptosis; cell death; nuclear export
Categories
Funding
- Investissements d'Avenir programme [ANR-11-IDEX-0005-02]
- Sorbonne Paris Cite
- Labex INFLAMEX
- Chancellerie des Universites de Paris (Legs Poix)
- DHU AUTHORS (AP-HP)
- DHU AUTHORS (Paris Descartes University)
- Association pour la Recherche sur le Cancer [ARC-PJA 20131200141]
- Vaincre La Mucoviscidose (VLM)
- ABCF2-Mucoviscidose and Arthritis Fondation Courtin
- Novartis
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The life span of a neutrophil is a tightly regulated process as extended survival is beneficial for pathogen elimination and cell death necessary to prevent cytotoxic content release from activated neutrophils at the inflammatory site. Therefore, the control between survival and death must be a dynamic process. We have previously described that proliferating cell nuclear antigen (PCNA) which is known as a nuclear protein pivotal in DNA synthesis, is a key element in controlling neutrophil survival through its association with procaspases. Contrary to the dogma which asserted that PCNA has a strictly nuclear function, in mature neutrophils, PCNA is present exclusively within the cytosol due to its nuclear export at the end of the granulocytic differentiation. More recent studies are consistent with the notion that the cytosolic scaffold of PCNA is aimed at modulating neutrophil fate rather than simply preventing death. Ultimately, targeting neutrophil survival might have important applications not just in the field of immunology and inflammation, but also in hematology and transfusion. The neutrophil emerges as a unique and powerful cellular model to unravel the basic mechanisms governing the cell cycle-independent functions of PCNA and should be considered as a leader of the pack.
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