Interferon regulatory factor 1 regulates PANoptosis to prevent colorectal cancer

Karki, Rajendra; Sharma, Bhesh Raj; Lee, Ein; Banoth, Balaji; Malireddi, R.K. Subbarao; Samir, Parimal; Tuladhar, Shraddha; Mummareddy, Harisankeerth; Burton, Amanda R.; Vogel, Peter; Kanneganti, Thirumala‐Devi

doi:10.1172/jci.insight.136720

Cited by 170 publications

(148 citation statements)

References 56 publications

(68 reference statements)

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“…During necroptosis, proteins containing a receptor interacting protein (RIP) homotypic interaction motif (RHIM), including RIP kinase 1 (RIPK1) and RIP kinase 3 (RIPK3), play crucial roles in the phosphorylation of the mixed lineage kinase domain-like pseudokinase (MLKL), which executes cell death (13,16). The identification of extensive crosstalk between pyroptosis, apoptosis, and necroptosis led to the establishment of the concept of "PANoptosis" (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). PANoptosis ('P', Pyroptosis; 'A', Apoptosis; 'N', Necroptosis; and 'optosis', a form of programmed cell death) is defined as "a unique inflammatory programmed cell death regulated by the PANoptosome, which provides a molecular scaffold that allows for interactions and activation of the machinery required for inflammasome/pyroptosis (such as NLRP3, ASC, caspase-1), apoptosis (caspase-8), and necroptosis (RIPK3/RIPK1)" (17,25,28,29).…”

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confidence: 99%

ZBP1 promotes fungi-induced inflammasome activation and pyroptosis, apoptosis, and necroptosis (PANoptosis)

Banoth¹,

Tuladhar²,

Karki

et al. 2020

Journal of Biological Chemistry

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114

101

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Candida albicans and Aspergillus fumigatus are dangerous fungal pathogens with high morbidity and mortality, particularly in immunocompromised patients. Innate immune-mediated programmed cell death (pyroptosis, apoptosis, necroptosis) is an integral part of host defense against pathogens. Inflammasomes, which are upstream of pyroptosis, have been characterized as key mediators of fungal sensing and drivers of proinflammatory responses. However, the specific cell death pathways and key upstream sensors activated in the context of Candida and Aspergillus infections are unknown. Here, we report that C. albicans and A. fumigatus infection induced inflammatory programmed cell death in the form of pyroptosis, apoptosis, and necroptosis (PANoptosis). Furthermore, we identified the innate immune sensor Z-DNA binding protein 1 (ZBP1) as the apical sensor of fungal infection responsible for activating the inflammasome/pyroptosis, apoptosis, and necroptosis. The Zα2 domain of ZBP1 was required to promote this inflammasome activation and PANoptosis. Overall, our results demonstrate that C. albicans and A. fumigatus induce PANoptosis and that ZBP1 plays a vital role in inflammasome activation, PANoptosis, and inflammation in response to fungal pathogens.

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mentioning

confidence: 99%

ZBP1 promotes fungi-induced inflammasome activation and pyroptosis, apoptosis, and necroptosis (PANoptosis)

Banoth¹,

Tuladhar²,

Karki

et al. 2020

Journal of Biological Chemistry

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114

101

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“…58,59 PANoptosis also has implications in cancer, as the regulation of PANoptosis by interferon-regulatory factor 1 (IRF1) prevents the development of colorectal cancer in a mouse model. 60 Overall, the process of PANoptosis has diverse implications throughout infectious and inflammatory diseases, development, and cancer.…”

Section: Panoptosismentioning

confidence: 99%

The regulation of the ZBP1‐NLRP3 inflammasome and its implications in pyroptosis, apoptosis, and necroptosis (PANoptosis)

Zheng

Kanneganti

2020

Immunological Reviews

273

172

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ZBP1 has been characterized as a critical innate immune sensor of not only viral RNA products but also endogenous nucleic acid ligands. ZBP1 sensing of the Z‐RNA produced during influenza virus infection induces cell death in the form of pyroptosis, apoptosis, and necroptosis (PANoptosis). PANoptosis is a coordinated cell death pathway that is driven through a multiprotein complex called the PANoptosome and enables crosstalk and co‐regulation among these processes. During influenza virus infection, a key step in PANoptosis and PANoptosome assembly is the formation of the ZBP1‐NLRP3 inflammasome. When Z‐RNA is sensed, ZBP1 recruits RIPK3 and caspase‐8 to activate the ZBP1‐NLRP3 inflammasome. Several other host factors have been found to be important for ZBP1‐NLRP3 inflammasome assembly, including molecules involved in the type I interferon signaling pathway and caspase‐6. Additionally, influenza viral proteins, such as M2, NS1, and PB1‐F2, have also been shown to regulate the ZBP1‐NLRP3 inflammasome. This review explains the functions of ZBP1 and the mechanistic details underlying the activation of the ZBP1‐NLRP3 inflammasome and the formation of the PANoptosome. Improved understanding of the ZBP1‐NLRP3 inflammasome will direct the development of therapeutic strategies to target infectious and inflammatory diseases.

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“…9 In our review, we detail the role of the ZBP1-NLRP3 inflammasome in inflammatory cell death and describe the concept of PANoptosis, which is defined as a unique inflammatory programmed cell death induced downstream of the PANoptosome. 7,[10][11][12][13][14][15][16][17][18][19][20][21][22] ZBP1 is critical for the formation of the ZBP1 PANoptosome to initiate PANoptosis in response to IAV. 10,19 The PANoptosome serves as a molecular scaffold, facilitating interactions between the machinery necessary for inflammasome activation/pyroptosis (such as NLRP3, ASC, caspase-1), apoptosis (caspase-8), and necroptosis (RIPK3/RIPK1).…”

Section: Nlrp3mentioning

confidence: 99%

“…Extensive crosstalk has been demonstrated between many cell death pathways, and this crosstalk led to the establishment of the concept of PANoptosis, defined as a unique inflammatory programmed cell death induced downstream of the PANoptosome. 7,[10][11][12][13][14][15][16][17][18][19][20][21][22] This complex provides a molecular scaffold that allows for interactions between the machinery required for inflammasome activation/pyroptosis (such as NLRP3, ASC, and caspase-1), apoptosis (caspase-8), and necroptosis (RIPK3/RIPK1). 10,17,19,21 The ability of these molecules to interact allows for intricate coregulation between the cell death pathways that had previously been thought to be independent.…”

Section: Cell De Athmentioning

confidence: 99%

“…PANoptosis has been implicated in infectious and autoinflammatory diseases, cancer, and beyond, and the molecular details and phenotypic outcomes of the crosstalk and coregulation among pyroptosis, apoptosis, and necroptosis are dependent on the stimulus provided. 7,10,12,13,15,[17][18][19] Recent studies demonstrated that PANoptosis is induced in response to Salmonella enterica serovar Typhimurium and the viral pathogens IAV and the coronavirus mouse hepatitis virus (MHV), among other pathogens; 7,9,10,19,22 however, it is increasingly clear that there are fun-…”

Section: Cell De Athmentioning

confidence: 99%

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Intracellular innate immune receptors: Life inside the cell

Kanneganti

2020

Immunological Reviews

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Interferon regulatory factor 1 regulates PANoptosis to prevent colorectal cancer

Cited by 170 publications

References 56 publications

ZBP1 promotes fungi-induced inflammasome activation and pyroptosis, apoptosis, and necroptosis (PANoptosis)

ZBP1 promotes fungi-induced inflammasome activation and pyroptosis, apoptosis, and necroptosis (PANoptosis)

The regulation of the ZBP1‐NLRP3 inflammasome and its implications in pyroptosis, apoptosis, and necroptosis (PANoptosis)

Intracellular innate immune receptors: Life inside the cell

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