c-Abl-Mediated Tyrosine Phosphorylation of PARP1 Is Crucial for Expression of Proinflammatory Genes.


Journal

Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Titre abrégé: J Immunol
Pays: United States
ID NLM: 2985117R

Informations de publication

Date de publication:
15 09 2019
Historique:
received: 11 12 2018
accepted: 07 05 2019
pubmed: 11 8 2019
medline: 16 5 2020
entrez: 11 8 2019
Statut: ppublish

Résumé

Poly(ADP-ribosyl)ation is a rapid and transient posttranslational protein modification mostly catalyzed by poly(ADP-ribose) polymerase-1 (PARP1). Fundamental roles of activated PARP1 in DNA damage repair and cellular response pathways are well established; however, the precise mechanisms by which PARP1 is activated independent of DNA damage, and thereby playing a role in expression of inflammatory genes, remain poorly understood. In this study, we show that, in response to LPS or TNF-α exposure, the nonreceptor tyrosine kinase c-Abl undergoes nuclear translocation and interacts with and phosphorylates PARP1 at the conserved Y829 site. Tyrosine-phosphorylated PARP1 is required for protein poly(ADP-ribosyl)ation of RelA/p65 and NF-κB-dependent expression of proinflammatory genes in murine RAW 264.7 macrophages, human monocytic THP1 cells, or mouse lungs. Furthermore, LPS-induced airway lung inflammation was reduced by inhibition of c-Abl activity. The present study elucidated a novel signaling pathway to activate PARP1 and regulate gene expression, suggesting that blocking the interaction of c-Abl with PARP1 or pharmaceutical inhibition of c-Abl may improve the outcomes of PARP1 activation-mediated inflammatory diseases.

Identifiants

pubmed: 31399520
pii: jimmunol.1801616
doi: 10.4049/jimmunol.1801616
pmc: PMC6731455
mid: NIHMS1529238
doi:

Substances chimiques

NF-kappa B 0
Tyrosine 42HK56048U
Parp1 protein, mouse EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1 EC 2.4.2.30

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1521-1531

Subventions

Organisme : NIAID NIH HHS
ID : P01 AI062885
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES018948
Pays : United States

Informations de copyright

Copyright © 2019 by The American Association of Immunologists, Inc.

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Auteurs

Ameer Ali Bohio (AA)

Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China.
School of Life Sciences, Northeast Normal University, Changchun 130024, China.

Aman Sattout (A)

Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China.
School of Life Sciences, Northeast Normal University, Changchun 130024, China.

Ruoxi Wang (R)

Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China.
School of Life Sciences, Northeast Normal University, Changchun 130024, China.

Ke Wang (K)

Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China.
School of Life Sciences, Northeast Normal University, Changchun 130024, China.

Rajiv Kumar Sah (RK)

Transgenic Research Center, School of Life Sciences, Northeast Normal University, Changchun 130024, China; and.

Xiaolan Guo (X)

Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China.
School of Life Sciences, Northeast Normal University, Changchun 130024, China.

Xianlu Zeng (X)

Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China.
School of Life Sciences, Northeast Normal University, Changchun 130024, China.

Yueshuang Ke (Y)

Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China.
School of Life Sciences, Northeast Normal University, Changchun 130024, China.

Istvan Boldogh (I)

Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555.

Xueqing Ba (X)

Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China; baxq755@nenu.edu.cn.
School of Life Sciences, Northeast Normal University, Changchun 130024, China.

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Classifications MeSH