NALPs: a novel protein family involved in inflammation

Tschopp, Jürg; Martinon, Fabio; Burns, Kimberly

doi:10.1038/nrm1019

Cited by 662 publications

(543 citation statements)

References 91 publications

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“…A more recent proposal suggests the name NACHT-LRR or NLR [9]. Several others reported on the pyrin-containing subgroup or members of this subgroup, which were given various names including PAN, PYPAF and NALP [10][11][12].…”

Section: The Caterpiller (Clr) Gene Familymentioning

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: The Caterpiller (Clr) Gene Familymentioning

confidence: 99%

“…The formation of this multiprotein complex leads to the activation of caspase-1 and subsequent production of mature IL-1β. These topics have been discussed in several recent reviews and will not be a focus here [12,14]. Instead, this review will focus on a pyrin-containing CLR protein which we refer to as Monarch-1.…”

Section: The Caterpiller (Clr) Gene Familymentioning

confidence: 99%

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

Lich

Ting

2007

Microbes and Infection

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“…Therefore, we cloned only the cDNA encoding the NACHT domain, which is responsible for selfinteraction of NALPs (reviewed by Tschopp et al 32 ), and the leucine-rich repeats (LRR). EBBP or the RFP domain, but not the BBCC domain, interacted with the NACHT domain, but not with the LRR domain of NALP1 ( Figure 2e and results not shown).…”

Section: Identification Of the Interaction Domains Of Ebbp And Its Bimentioning

confidence: 99%

The estrogen-responsive B box protein: a novel enhancer of interleukin-1β secretion

et al. 2006

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The estrogen-responsive B box protein (EBBP) and Pyrin belong to a family of structurally related proteins. While mutations in the pyrin gene cause an autoinflammatory disease, the biological function of EBBP is unknown. In this study, we identified the proinflammatory cytokine interleukin1b (IL-1b) as an EBBP-binding partner. Furthermore, caspase-1 and NACHT, LRR and Pyrin domain containing protein (NALP) 1, two components of the recently identified inflammasome, a platform for the activation of caspase-1, also interact with EBBP. These proteins bind to the RFP domain of EBBP, suggesting that this domain of so far unknown function is an important protein-binding domain. EBBP was secreted in a caspase-1-dependent manner from cultured cells, and its secretion was enhanced by IL-1b. Vice versa, endogenous and overerexpressed EBBP increased IL-1b secretion. These results provide evidence for a role of EBBP in innate immunity by enhancing the alternative secretion pathway of IL-1b.

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“…The pyrin domain (PYD)-containing proteins pyrin (also known as marenostrin) and cryopyrin (also known as Pypaf1, Nalp3), have been implicated in the etiology of a number of inflammatory diseases in humans termed hereditary periodic fever syndromes (PFSs) (reviewed in Gumucio et al, 1 Hull et al, 2 McDermott and Aksentijevich, 3 Stehlik and Reed 4 and Tschopp 5 ). Mutations in the MEFV gene which encodes pyrin are associated with familial Mediterranean fever (FMF), 6,7 while mutations in the CIAS1 gene which encodes cryopyrin are responsible for three PFSs; familial cold autoinflammatory syndrome (FCAS)/familial cold urticaria (FCU), Muckle-Wells syndrome (MWS), and neonatalonset multisystem inflammatory disease (NOMID)/chronic infantile neurological cutaneous and articular syndrome (CIN-CA).…”

Section: Introductionmentioning

confidence: 99%

Cryopyrin and pyrin activate caspase-1, but not NF-κB, via ASC oligomerization

et al. 2005

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Mutations in cryopyrin and pyrin proteins are responsible for several autoinflammatory disorders in humans, suggesting that these proteins play important roles in regulating inflammation. Using a HEK293 cell-based reconstitution system that stably expresses ASC and procaspase-1 we demonstrated that neither cryopyrin nor pyrin or their corresponding disease-associated mutants could significantly activate NF-jB in this system. However, both cryopyrin and two disease-associated cryopyrin mutants induced ASC oligomerization and ASC-dependent caspase-1 activation, with the disease-associated mutants being more potent than the wild-type (WT) cryopyrin, because of increased selfoligomerization. Contrary to the proposed anti-inflammatory activity of WT pyrin, our results demonstrated that pyrin, like cryopyrin, can also assemble an inflammasome complex with ASC and procaspase-1 leading to ASC oligomerization, caspase-1 activation and interleukin-1b processing. Thus, we propose that pyrin could function as a proinflammatory molecule.

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NALPs: a novel protein family involved in inflammation

Cited by 662 publications

References 91 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

The estrogen-responsive B box protein: a novel enhancer of interleukin-1β secretion

Cryopyrin and pyrin activate caspase-1, but not NF-κB, via ASC oligomerization

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