PARP14 controls the nuclear accumulation of a subset of type i IFN-inducible proteins

Greta Caprara, Elena Prosperini, Viviana Piccolo, Gianluca Sigismondo, Alessia Melacarne, Alessandro Cuomo, Mark Boothby, Maria Rescigno, Tiziana Bonaldi, Gioacchino Natoli

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The enzymes of the poly-ADP-ribose polymerase (PARP) superfamily control many relevant cellular processes, but a precise understanding of their activities in different physiological or disease contexts is largely incomplete. We found that transcription of several Parp genes was dynamically regulated upon murine macrophage activation by endotoxin. PARP14 was strongly induced by several inflammatory stimuli and translocated into the nucleus of stimulated cells. Quantitative mass spectrometry analysis showed that PARP14 bound to a group of IFN-stimulated gene (ISG)-encoded proteins, most with an unknown function, and it was required for their nuclear accumulation. Moreover, PARP14 depletion attenuated transcription of primary antiviral response genes regulated by the IFN regulatory transcription factor 3, including Ifnb1, thus reducing IFN-b production and activation of ISGs involved in the secondary antiviral response. In agreement with the above-mentioned data, PARP14 hindered Salmonella typhimurium proliferation in murine macrophages. Overall, these data hint at a role of PARP14 in the control of antimicrobial responses and specifically in nuclear activities of a subgroup of ISG-encoded proteins.

Original languageEnglish
Pages (from-to)2439-2454
Number of pages16
JournalJournal of Immunology
Volume200
Issue number7
DOIs
Publication statusPublished - Apr 1 2018

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Antiviral Agents
Interferon Regulatory Factor-3
Transcription Factor 3
Poly(ADP-ribose) Polymerases
Macrophage Activation
Salmonella typhimurium
Cell Nucleus
Endotoxins
Genes
Mass Spectrometry
Proteins
Macrophages
Enzymes

ASJC Scopus subject areas

  • Immunology

Cite this

PARP14 controls the nuclear accumulation of a subset of type i IFN-inducible proteins. / Caprara, Greta; Prosperini, Elena; Piccolo, Viviana; Sigismondo, Gianluca; Melacarne, Alessia; Cuomo, Alessandro; Boothby, Mark; Rescigno, Maria; Bonaldi, Tiziana; Natoli, Gioacchino.

In: Journal of Immunology, Vol. 200, No. 7, 01.04.2018, p. 2439-2454.

Research output: Contribution to journalArticle

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AU - Melacarne, Alessia

AU - Cuomo, Alessandro

AU - Boothby, Mark

AU - Rescigno, Maria

AU - Bonaldi, Tiziana

AU - Natoli, Gioacchino

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AB - The enzymes of the poly-ADP-ribose polymerase (PARP) superfamily control many relevant cellular processes, but a precise understanding of their activities in different physiological or disease contexts is largely incomplete. We found that transcription of several Parp genes was dynamically regulated upon murine macrophage activation by endotoxin. PARP14 was strongly induced by several inflammatory stimuli and translocated into the nucleus of stimulated cells. Quantitative mass spectrometry analysis showed that PARP14 bound to a group of IFN-stimulated gene (ISG)-encoded proteins, most with an unknown function, and it was required for their nuclear accumulation. Moreover, PARP14 depletion attenuated transcription of primary antiviral response genes regulated by the IFN regulatory transcription factor 3, including Ifnb1, thus reducing IFN-b production and activation of ISGs involved in the secondary antiviral response. In agreement with the above-mentioned data, PARP14 hindered Salmonella typhimurium proliferation in murine macrophages. Overall, these data hint at a role of PARP14 in the control of antimicrobial responses and specifically in nuclear activities of a subgroup of ISG-encoded proteins.

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