New insights into nucleic acid sensor AIM2: The potential benefit in targeted therapy for cancer
The AIM2 inflammasome represents a multifaceted oligomeric protein complex within the innate immune system, with the capacity to perceive double-stranded DNA (dsDNA) and engage in diverse physiological reactions and disease contexts, including cancer. While originally conceived as a discerning DNA s...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Pharmacological Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661824000239 |
| _version_ | 1827356730046021632 |
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| author | Jian-Zhou Cui Zhi Huan Chew Lina H.K. Lim |
| author_facet | Jian-Zhou Cui Zhi Huan Chew Lina H.K. Lim |
| author_sort | Jian-Zhou Cui |
| collection | DOAJ |
| description | The AIM2 inflammasome represents a multifaceted oligomeric protein complex within the innate immune system, with the capacity to perceive double-stranded DNA (dsDNA) and engage in diverse physiological reactions and disease contexts, including cancer. While originally conceived as a discerning DNA sensor, AIM2 has demonstrated its capability to discern various nucleic acid variations, encompassing RNA and DNA-RNA hybrids. Through its interaction with nucleic acids, AIM2 orchestrates the assembly of a complex involving multiple proteins, aptly named the AIM2 inflammasome, which facilitates the enzymatic cleavage of proinflammatory cytokines, namely pro-IL-1β and pro-IL-18. This process, in turn, underpins its pivotal biological role. In this review, we provide a systematic summary and discussion of the latest advancements in AIM2 sensing various types of nucleic acids. Additionally, we discuss the modulation of AIM2 activation, which can cause cell death, including pyroptosis, apoptosis, and autophagic cell death. Finally, we fully illustrate the evidence for the dual role of AIM2 in different cancer types, including both anti-tumorigenic and pro-tumorigenic functions. Considering the above information, we uncover the therapeutic promise of modulating the AIM2 inflammasome in cancer treatment. |
| first_indexed | 2024-03-08T05:14:11Z |
| format | Article |
| id | doaj.art-74ef71f974584448b53ae9e736cbb75e |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2024-03-08T05:14:11Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj.art-74ef71f974584448b53ae9e736cbb75e2024-02-07T04:42:33ZengElsevierPharmacological Research1096-11862024-02-01200107079New insights into nucleic acid sensor AIM2: The potential benefit in targeted therapy for cancerJian-Zhou Cui0Zhi Huan Chew1Lina H.K. Lim2Translational Immunology Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; NUS Immunology Program, Life Sciences Institute, National University of Singapore, Singapore; NUS-Cambridge Immunophenotyping Centre, Life Science Institute, National University of Singapore, Singapore; Correspondence to: Immunology Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), 28 Medical Drive, Life Sciences Institute #03‑06C and #03‑06J, Singapore 117456, Singapore.Translational Immunology Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; NUS Immunology Program, Life Sciences Institute, National University of Singapore, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore; Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, SingaporeTranslational Immunology Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; NUS Immunology Program, Life Sciences Institute, National University of Singapore, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Correspondence to: Immunology Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), 28 Medical Drive, Life Sciences Institute #03‑06C and #03‑06J, Singapore 117456, Singapore.The AIM2 inflammasome represents a multifaceted oligomeric protein complex within the innate immune system, with the capacity to perceive double-stranded DNA (dsDNA) and engage in diverse physiological reactions and disease contexts, including cancer. While originally conceived as a discerning DNA sensor, AIM2 has demonstrated its capability to discern various nucleic acid variations, encompassing RNA and DNA-RNA hybrids. Through its interaction with nucleic acids, AIM2 orchestrates the assembly of a complex involving multiple proteins, aptly named the AIM2 inflammasome, which facilitates the enzymatic cleavage of proinflammatory cytokines, namely pro-IL-1β and pro-IL-18. This process, in turn, underpins its pivotal biological role. In this review, we provide a systematic summary and discussion of the latest advancements in AIM2 sensing various types of nucleic acids. Additionally, we discuss the modulation of AIM2 activation, which can cause cell death, including pyroptosis, apoptosis, and autophagic cell death. Finally, we fully illustrate the evidence for the dual role of AIM2 in different cancer types, including both anti-tumorigenic and pro-tumorigenic functions. Considering the above information, we uncover the therapeutic promise of modulating the AIM2 inflammasome in cancer treatment.http://www.sciencedirect.com/science/article/pii/S1043661824000239AIM2 InflammasomeCytosolic DNAPyroptosisImmunotherapyDNA-RNA HybridsPD-L1 |
| spellingShingle | Jian-Zhou Cui Zhi Huan Chew Lina H.K. Lim New insights into nucleic acid sensor AIM2: The potential benefit in targeted therapy for cancer Pharmacological Research AIM2 Inflammasome Cytosolic DNA Pyroptosis Immunotherapy DNA-RNA Hybrids PD-L1 |
| title | New insights into nucleic acid sensor AIM2: The potential benefit in targeted therapy for cancer |
| title_full | New insights into nucleic acid sensor AIM2: The potential benefit in targeted therapy for cancer |
| title_fullStr | New insights into nucleic acid sensor AIM2: The potential benefit in targeted therapy for cancer |
| title_full_unstemmed | New insights into nucleic acid sensor AIM2: The potential benefit in targeted therapy for cancer |
| title_short | New insights into nucleic acid sensor AIM2: The potential benefit in targeted therapy for cancer |
| title_sort | new insights into nucleic acid sensor aim2 the potential benefit in targeted therapy for cancer |
| topic | AIM2 Inflammasome Cytosolic DNA Pyroptosis Immunotherapy DNA-RNA Hybrids PD-L1 |
| url | http://www.sciencedirect.com/science/article/pii/S1043661824000239 |
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