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PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation

Author

Listed:
  • Hiroshi Iwata

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School)

  • Claudia Goettsch

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School)

  • Amitabh Sharma

    (Brigham and Women's Hospital, Harvard Medical School
    Center for Complex Network Research, Northeastern University)

  • Piero Ricchiuto

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School)

  • Wilson Wen Bin Goh

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School)

  • Arda Halu

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School
    Brigham and Women's Hospital, Harvard Medical School)

  • Iwao Yamada

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School)

  • Hideo Yoshida

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School)

  • Takuya Hara

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School)

  • Mei Wei

    (Vanderbilt University School of Medicine)

  • Noriyuki Inoue

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School)

  • Daiju Fukuda

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School)

  • Alexander Mojcher

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School)

  • Peter C. Mattson

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School)

  • Albert-László Barabási

    (Brigham and Women's Hospital, Harvard Medical School
    Center for Complex Network Research, Northeastern University)

  • Mark Boothby

    (Vanderbilt University School of Medicine)

  • Elena Aikawa

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School
    Center for Excellence in Vascular Biology, Brigham and Women’s Hospital, Harvard Medical School)

  • Sasha A. Singh

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School)

  • Masanori Aikawa

    (Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women’s Hospital, Harvard Medical School
    Brigham and Women's Hospital, Harvard Medical School
    Center for Excellence in Vascular Biology, Brigham and Women’s Hospital, Harvard Medical School)

Abstract

Despite the global impact of macrophage activation in vascular disease, the underlying mechanisms remain obscure. Here we show, with global proteomic analysis of macrophage cell lines treated with either IFNγ or IL-4, that PARP9 and PARP14 regulate macrophage activation. In primary macrophages, PARP9 and PARP14 have opposing roles in macrophage activation. PARP14 silencing induces pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells, whereas it suppresses anti-inflammatory gene expression and STAT6 phosphorylation in M(IL-4) cells. PARP9 silencing suppresses pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells. PARP14 induces ADP-ribosylation of STAT1, which is suppressed by PARP9. Mutations at these ADP-ribosylation sites lead to increased phosphorylation. Network analysis links PARP9–PARP14 with human coronary artery disease. PARP14 deficiency in haematopoietic cells accelerates the development and inflammatory burden of acute and chronic arterial lesions in mice. These findings suggest that PARP9 and PARP14 cross-regulate macrophage activation.

Suggested Citation

  • Hiroshi Iwata & Claudia Goettsch & Amitabh Sharma & Piero Ricchiuto & Wilson Wen Bin Goh & Arda Halu & Iwao Yamada & Hideo Yoshida & Takuya Hara & Mei Wei & Noriyuki Inoue & Daiju Fukuda & Alexander M, 2016. "PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation," Nature Communications, Nature, vol. 7(1), pages 1-19, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12849
    DOI: 10.1038/ncomms12849
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    Cited by:

    1. Ashna Dhoonmoon & Claudia M. Nicolae & George-Lucian Moldovan, 2022. "The KU-PARP14 axis differentially regulates DNA resection at stalled replication forks by MRE11 and EXO1," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Chun Wai Wong & Christos Evangelou & Kieran N. Sefton & Rotem Leshem & Wei Zhang & Vishaka Gopalan & Sorayut Chattrakarn & Macarena Lucia Fernandez Carro & Erez Uzuner & Holly Mole & Daniel J. Wilcock, 2023. "PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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