ZBP1 condensate formation synergizes Z-NAs recognition and signal transduction DOI Creative Commons

Feiyan Xie,

Di Wu, Jing Huang

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(7)

Published: July 9, 2024

Abstract Z-DNA binding protein 1 (ZBP1) is a crucial player in the intracellular recognition of Z-form nucleic acids (Z-NAs) through its Zαβ domain, initiating downstream interactions with RIPK1 and RIPK3 via RHIM domains. This engagement leads to assembly PANoptosomes, ultimately inducing programmed cell death curb pathogen dissemination. How domain cooperate trigger Z-NAs signal transduction remains unclear. Here, we show that ZBP1 condensate formation facilitates antiviral transduction. The dimerizes concentration-dependent manner, forming characteristic condensates solutions evidenced by DLS SAXS methods. exhibits preference for 10-bp length CG (10CG) DNA Z-RNA ligand, which turn enhanced dimerization, expediting droplet vitro amyloid-like puncta cells. Subsequent investigations reveal could form liquid-liquid phase separation property upon HSV IAV infections, while full-length forms or without infections. Furthermore, domains typical amyloidal fibril characterizations cross-polymerize depending on core motif 206 IQIG 209 , mutated impede necroptosis immunity HT-29 Thus, viral activation synergic action different domains, revealing elaborated mechanism innate immunity.

Language: Английский

Innate immune inflammatory cell death: PANoptosis and PANoptosomes in host defense and disease DOI Open Access
Wen Chen, Jessica M. Gullett, Rebecca E. Tweedell

et al.

European Journal of Immunology, Journal Year: 2023, Volume and Issue: 53(11)

Published: Feb. 13, 2023

Regulated cell death (RCD) triggered by innate immune activation is an important strategy for host survival during pathogen invasion and perturbations of cellular homeostasis. There are two main categories RCD, including nonlytic lytic pathways. Apoptosis the most well-characterized inflammatory pyroptosis necroptosis pathways among best known forms. While these were historically viewed as independent RCD pathways, extensive evidence cross-talk their molecular components created a knowledge gap in our mechanistic understanding pathway components, which led to identification PANoptosis. PANoptosis unique that regulated PANoptosome complexes upon sensing pathogens, pathogen-associated patterns (PAMPs), damage-associated (DAMPs) or cytokines produced downstream. Cytosolic sensors regulators, such ZBP1, AIM2 RIPK1, promote assembly PANoptosomes drive In this review, we discuss highlight mechanisms assembly, regulation identified date. We also how mutations linked diseases. Given impact specifically, across disease spectrum, improved will be critical identifying new therapeutic targets strategies.

Language: Английский

Citations

76
Regulated cell death pathways and their roles in homeostasis, infection, inflammation, and tumorigenesis DOI Creative Commons

Ein Lee,

Chang‐Hyun Song, Sung‐Jin Bae

et al.

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(8), P. 1632 - 1643

Published: Aug. 23, 2023

Pyroptosis, apoptosis, necroptosis, and ferroptosis, which are the most well-studied regulated cell death (RCD) pathways, contribute to clearance of infected or potentially neoplastic cells, highlighting their importance in homeostasis, host defense against pathogens, cancer, a wide range other pathologies. Although these four RCD pathways employ distinct molecular cellular processes, emerging genetic biochemical studies have suggested remarkable flexibility crosstalk among them. The pyroptosis, apoptosis necroptosis is more evident responses infection, has led conceptualization PANoptosis. In this review, we provide brief overview mechanisms ferroptosis maintaining homeostasis. We discuss intricate current evidence supporting PANoptosis, focusing on infectious diseases cancer. Understanding fundamental processes various crucial inform development new therapeutics many diseases, including sterile inflammation,

Language: Английский

Citations

49
PANoptosis: bridging apoptosis, pyroptosis, and necroptosis in cancer progression and treatment DOI Creative Commons
Jie Gao,

Anying Xiong,

Jiliu Liu

et al.

Cancer Gene Therapy, Journal Year: 2024, Volume and Issue: 31(7), P. 970 - 983

Published: March 29, 2024

Abstract This comprehensive review explores the intricate mechanisms of PANoptosis and its implications in cancer. PANoptosis, a convergence apoptosis, pyroptosis, necroptosis, plays crucial role cell death immune response regulation. The study delves into molecular pathways each mechanism their crosstalk within emphasizing shared components like caspases PANoptosome complex. It highlights significant various cancers, including respiratory, digestive, genitourinary, gliomas, breast showing impact on tumorigenesis patient survival rates. We further discuss interwoven relationship between tumor microenvironment (TME), illustrating how influences behavior progression. underscores dynamic interplay tumors microenvironments, focusing roles different cells interactions with cancer cells. Moreover, presents new breakthroughs therapy, potential targeting to enhance anti-tumor immunity. outlines strategies manipulate for therapeutic purposes, such as key signaling molecules caspases, NLRP3, RIPK1, RIPK3. novel treatments immunogenic PANoptosis-initiated therapies nanoparticle-based is also explored.

Language: Английский

Citations

35
RIPK3 signaling and its role in regulated cell death and diseases DOI Creative Commons
Yaqi Zhou, Yaxuan Xiang, S. Liu

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: April 29, 2024

Abstract Receptor-interacting protein kinase 3 (RIPK3), a member of the receptor-interacting (RIPK) family with serine/threonine activity, interacts RIPK1 to generate necrosomes, which trigger caspase-independent programmed necrosis. As vital component RIPK3 plays an indispensable role in necroptosis, is crucial for human life and health. In addition, participates pathological process several infections, aseptic inflammatory diseases, tumors (including tumor-promoting -suppressive activities) by regulating autophagy, cell proliferation, metabolism production chemokines/cytokines. This review summarizes recent research progress regulators signaling pathway discusses potential RIPK3/necroptosis aetiopathogenesis various diseases. An in-depth understanding mechanisms functions may facilitate development novel therapeutic strategies.

Language: Английский

Citations

20
Modulating NLRP3 Inflammasomes in Idiopathic Pulmonary Fibrosis: A Comprehensive Review on Flavonoid-Based Interventions DOI Creative Commons
Megh Pravin Vithalkar, Shaili Pradhan, K. Sandra

et al.

Cell Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Abstract Idiopathic Pulmonary Fibrosis (IPF) is a severe, rapidly advancing disease that drastically diminishes life expectancy. Without treatment, it can progress to lung cancer. The precise etiology of IPF remains unknown, but inflammation and damage the alveolar epithelium are widely thought be pivotal in its development. Research has indicated activating NLRP3 inflammasome crucial mechanism pathogenesis, as triggers release pro-inflammatory cytokines such IL-1β, IL-18, TGF-β. These contribute myofibroblast differentiation extracellular matrix (ECM) accumulation. Currently, treatment options for limited. Only two FDA-approved medications, pirfenidone nintedanib, available. While these drugs decelerate progression, they come with range side effects do not cure disease. Additional strategies primarily involve supportive care therapy. Emerging research highlighted numerous flavonoids derived from traditional medicines inhibit critical regulators responsible inflammasome. show promise potential therapeutic agents managing IPF, offering new avenue targets core inflammatory processes this debilitating condition. Graphical

Language: Английский

Citations

2
Novel insights into double-stranded RNA-mediated immunopathology DOI
Richard de Reuver, Jonathan Maelfait

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 24(4), P. 235 - 249

Published: Sept. 26, 2023

Language: Английский

Citations

30
Innate immune sensing of cell death in disease and therapeutics DOI
Si Ming Man, Thirumala‐Devi Kanneganti

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(9), P. 1420 - 1433

Published: Sept. 1, 2024

Language: Английский

Citations

14
Structurally Specific Z-DNA Proteolysis Targeting Chimera Enables Targeted Degradation of Adenosine Deaminase Acting on RNA 1 DOI
Zhen Wang, Dingpeng Zhang, Xing Qiu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(11), P. 7584 - 7593

Published: March 12, 2024

Given the prevalent advancements in DNA- and RNA-based PROTACs, there remains a significant need for exploration expansion of more specific DNA-based tools, thus broadening scope repertoire PROTACs. Unlike conventional A- or B-form DNA, Z-form DNA is configuration that exclusively manifests itself under stress conditions with target sequences, which can be recognized by reader proteins, such as ADAR1 ZBP1, to exert downstream biological functions. The core our innovation lies strategic engagement its degradation achieved leveraging VHL ligand conjugated recruit E3 ligase. This ingenious construct engendered series Z-PROTACs, we utilized selectively degrade Z-DNA-binding protein ADAR1, molecule frequently overexpressed cancer cells. meticulously orchestrated approach triggers cascade PANoptotic events, notably encompassing apoptosis necroptosis, mitigating blocking effect on particularly cells compared normal Moreover, Z-PROTAC design exhibits pronounced predilection opposed other Z-DNA readers, ZBP1. As such, likely elicits positive immunological response, subsequently leading synergistic augmentation cell death. In summary, Z-DNA-based PROTAC (Z-PROTAC) introduces modality generated conformational change from B- harnesses structural specificity intrinsic potentiate selective strategy. methodology an inspiring conduit advancement PROTAC-based therapeutic modalities, underscoring potential selectivity within landscape PROTACs undruggable proteins.

Language: Английский

Citations

13
RNA editing enzymes: structure, biological functions and applications DOI Creative Commons
Dejiu Zhang,

Lei Zhu,

Yanyan Gao

et al.

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 16, 2024

Abstract With the advancement of sequencing technologies and bioinformatics, over than 170 different RNA modifications have been identified. However, only a few these can lead to base pair changes, which are called editing. editing is ubiquitous modification in mammalian transcriptomes an important co/posttranscriptional that plays crucial role various cellular processes. There two main types events: adenosine inosine (A-to-I) editing, catalyzed by ADARs on double-stranded or ADATs tRNA, cytosine uridine (C-to-U) APOBECs. This article provides overview structure, function, applications enzymes. We discuss structural characteristics three enzyme families their catalytic mechanisms also explain biological particularly innate immunity, cancer biogenesis, antiviral activity. Additionally, this describes tools for manipulating correct disease-causing mutations, as well potential enzymes field biotechnology therapy.

Language: Английский

Citations

12
ZBP1-mediated PANoptosis: A possible novel mechanism underlying the therapeutic effects of penehyclidine hydrochloride on myocardial ischemia–reperfusion injury DOI
Boqun Cui, Zeyou Qi, Wenjun Liu

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 137, P. 112373 - 112373

Published: June 12, 2024

Language: Английский

Citations

10