PAN1/NALP2/PYPAF2, an Inducible Inflammatory Mediator That Regulates NF-κB and Caspase-1 Activation in Macrophages

Bruey, Jean Marie; Bruey-Sédano, Nathalie; Newman, Ruchi M.; Chandler, Sharon; Stehlik, Christian; Reed, John C.

doi:10.1074/jbc.m406741200

Cited by 145 publications

(124 citation statements)

References 45 publications

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“…This was shown directly in reporter gene assays and indirectly in THP-1 monocytes, where siRNA mediated silencing of PYPAF2 results in increased expression of ICAM1. It appears that PYPAF2 performs this function through its association with the IKK complex [19]. In addition to the IKK complex, PYPAF2 also associates with ASC.…”

Section: Other Negative Regulatory Clr Proteinsmentioning

confidence: 99%

“…Inhibition of NF-κB is not unique to Monarch-1. Indeed, this phenotype is shared among several CLR proteins such as PYPAF2 and CLR16.2 [19,20]. Unfortunately, little is known regarding the molecular mechanisms by which Monarch-1 or these other CLR proteins exert this anti-inflammatory activity.…”

Section: Toward Identifying the Molecular Mechanisms Of Monarch-1 Actmentioning

confidence: 99%

“…For instance, NOD2 associates with TAK1 and inhibits the ability of TAK1 to activate NF-κB [28]. Similarly, PYPAF2 associates with ASC and the IKK complex and prevents NF-κB activation downstream of a number of activators [19]. It remains to be seen if these CLR proteins mediate NF-κB suppression through proteasome-mediated pathways.…”

Section: Toward Identifying the Molecular Mechanisms Of Monarch-1 Actmentioning

confidence: 99%

“…PYPAF2 is expressed more broadly than CLR16.2 or Monarch-1 and mRNA can be detected in many different cell types and tissues, including non-hematopoietic cells [19,29]. In addition, distinct from Monarch-1 and CLR16.2, PYPAF2 expression is induced following treatment of cells with LPS or proinflammatory cytokines.…”

Section: Other Negative Regulatory Clr Proteinsmentioning

confidence: 99%

“…However there is some concern surrounding such overexpression systems, as genes of this family have exhibited both positive and negative functions, depending on the dosage used. For instance, Bruey et al found that PYAPF2 enhances ASC-mediated IL-1β release at low doses [19]. This effect was lost as increasing amounts of PYPAF2 were expressed.…”

Section: Current Challenges and Future Directionsmentioning

confidence: 99%

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Monarch-1/PYPAF7 and other CATERPILLER (CLR, NOD, NLR) proteins with negative regulatory functions

Lich

Ting

2007

Microbes and Infection

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CATERPILLER is a mammalian gene family with signature NBD and LRR domains. Several members of this family are positive regulators of inflammatory responses. Others, however, exert negative effects on proinflammatory responses. These data are particularly convincing when shRNA/ siRNA are used. This review focuses on the Monarch-1/PYPAF7 gene with brief discussions of CLR16.2/NOD3, PYPAF2/PAN1/NALP2, and PYPAF3.

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Section: Other Negative Regulatory Clr Proteinsmentioning

confidence: 99%

Section: Toward Identifying the Molecular Mechanisms Of Monarch-1 Actmentioning

confidence: 99%

Section: Toward Identifying the Molecular Mechanisms Of Monarch-1 Actmentioning

confidence: 99%

Section: Other Negative Regulatory Clr Proteinsmentioning

confidence: 99%

Section: Current Challenges and Future Directionsmentioning

confidence: 99%

See 3 more Smart Citations

Monarch-1/PYPAF7 and other CATERPILLER (CLR, NOD, NLR) proteins with negative regulatory functions

Lich

Ting

2007

Microbes and Infection

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NOD‐Like Receptors

Arnold

Kienes

Sowa

et al. 2018

Encyclopedia of Life Sciences

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NOD‐like receptors (NLRs) are a family of pattern recognition receptors (PRRs), able to respond to conserved microbial structures and endogenous danger signals. NLRs modulate the inflammatory response via multiple pathways including NFκB (nuclear factor kappa‐light chain‐enhancer of activated B cells)‐activation, MAPKs, ERK and inflammasome formation, which results in IL‐1β release. They act in synergy with other PRRs, bridging innate to adaptive immunity. Moreover, some NLRs directly modulate adaptive immunity via transcriptional regulation of MHC (major histocompatibility complex) class I and class II. Their essential role in orchestrating inflammatory responses is seen via their association with morbidity. NLR dysfunction can result in cancer and autoinflammatory diseases, such as Crohn's disease and ulcerative colitis, pointing out their important role in maintaining gut homeostasis. Key Concepts NLRs are an intracellular subclass of PRRs that recognise microbe‐associated molecular patterns (MAMPs) and danger‐associated molecular patterns (DAMPs). NLRs are found in different animal species and have homologues in plants. NLRs share a common tripartite structure, typically consisting of an N ‐terminal domain from the death‐fold family, a central NACHT domain and a variable number of C ‐terminal LRRs. Activation of NLRs primes innate and adaptive immunity and drives the expression of MHC class I and class II genes. Some NLRs form inflammasomes, multiprotein platforms for caspase‐1 activation and IL‐1β release. NLRs maintain gut homeostasis, differentiating between commensals and pathogens. Mutations in NLRs can lead to severe autoinflammatory diseases, cancer, dysregulation of gut homeostasis and innate immune responses. Evidence suggests that some NLRs are further implicated in development. The function of some of the 22 human NLR proteins remains elusive.

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NLRP2 inhibits cell proliferation and migration by regulating EMT in lung adenocarcinoma cells

Mao

et al. 2022

Cell Biology International

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Nucleotide-binding oligomerization domain-like receptors (NLRs) are crucial types of innate immune sensors and well known for their critical roles in the immune system. However, how NLRP2 functions in the progression of cancer is largely unknown.Here, we identified NLRP2 as an antioncogene in lung adenocarcinoma (LUAD) cells. Gain-and loss-of-function studies revealed that NLRP2 silencing promoted cell proliferation and migration by stimulating NF-kB signaling in the microenvironment, which induced epithelial-to-mesenchymal transition (EMT) phenotype and cytoskeleton reorganization in LUAD cells. The addition of the NF-kB inhibitor rescued the function of NLRP2 on EMT. Moreover, NLRP2 increased the level of cofilin phosphorylation and repressed subsequent F-actin reorganization. Consistently, the in vivo study showed that NLRP2 played an inhibitory role in forming metastasis foci. Taken together, NLRP2 inhibited cell proliferation and migration by regulating EMT in LUAD cells, demonstrating the essential function of NLRP2 in the development of LUAD.

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PAN1/NALP2/PYPAF2, an Inducible Inflammatory Mediator That Regulates NF-κB and Caspase-1 Activation in Macrophages

Cited by 145 publications

References 45 publications

Monarch-1/PYPAF7 and other CATERPILLER (CLR, NOD, NLR) proteins with negative regulatory functions

Monarch-1/PYPAF7 and other CATERPILLER (CLR, NOD, NLR) proteins with negative regulatory functions

NOD‐Like Receptors

NLRP2 inhibits cell proliferation and migration by regulating EMT in lung adenocarcinoma cells

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