Inflammasome protein scaffolds the DNA damage complex during tumor development.

Autor: Shen C; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia., Pandey A; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia., Enosi Tuipulotu D; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia., Mathur A; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia., Liu L; Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.; ARC Centre of Excellence for the Mathematical Analysis of Cellular Systems, Canberra, Australian Capital Territory, Australia., Yang H; Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.; ARC Centre of Excellence for the Mathematical Analysis of Cellular Systems, Canberra, Australian Capital Territory, Australia., Adikari NK; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia., Ngo C; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia., Jing W; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia., Feng S; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia., Hao Y; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia., Zhao A; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia., Kirkby M; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia., Kurera M; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia., Zhang J; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia., Venkataraman S; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia., Liu C; Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.; School of Medicine, University of Queensland, Herston, Queensland, Australia.; Mater Pathology, Mater Hospital, South Brisbane, Queensland, Australia., Song R; Epigenetics and RNA Biology Laboratory, The School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia., Wong JJ; Epigenetics and RNA Biology Laboratory, The School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia., Schumann U; The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.; The Shine Dalgarno Centre for RNA Innovation, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.; The Save Sight Institute, The University of Sydney, Sydney, New South Wales, Australia., Natoli R; The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.; The Shine Dalgarno Centre for RNA Innovation, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.; School of Medicine and Psychology, The Australian National University, Canberra, Australian Capital Territory, Australia., Wen J; Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.; ARC Centre of Excellence for the Mathematical Analysis of Cellular Systems, Canberra, Australian Capital Territory, Australia., Zhang L; Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, OR, USA., Kaakoush NO; School of Biomedical Sciences, University of New South Wales Sydney, Sydney, New South Wales, Australia., Man SM; Division of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia. siming.man@anu.edu.au.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 Nov; Vol. 25 (11), pp. 2085-2096. Date of Electronic Publication: 2024 Oct 14.
DOI: 10.1038/s41590-024-01988-6
Abstrakt: Inflammasome sensors activate cellular signaling machineries to drive inflammation and cell death processes. Inflammasomes also control the development of certain diseases independently of canonical functions. Here, we show that the inflammasome protein NLR family CARD domain-containing protein 4 (NLRC4) attenuated the development of tumors in the Apc min/+ mouse model. This response was independent of inflammasome signaling by NLRP3, NLRP6, NLR family apoptosis inhibitory proteins, absent in melanoma 2, apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1 and caspase-11. NLRC4 interacted with the DNA-damage-sensing ataxia telangiectasia and Rad3-related (ATR)-ATR-interacting protein (ATRIP)-Ewing tumor-associated antigen 1 (ETAA1) complex to promote the recruitment of the checkpoint adapter protein claspin, licensing the activation of the kinase checkpoint kinase-1 (CHK1). Genotoxicity-induced activation of the NLRC4-ATR-ATRIP-ETAA1 complex drove the tumor-suppressing DNA damage response and CHK1 activation, and further attenuated the accumulation of DNA damage. These findings demonstrate a noninflammatory function of an inflammasome protein in promoting the DNA damage response and mediating protection against cancer.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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