The PYRIN Domain in Signal Transduction

Stehlik, Christian

doi:10.2174/138920307780831857

Cited by 24 publications

(22 citation statements)

References 213 publications

(357 reference statements)

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“…The PYD, also referred to as PAAD or DAPIN, is a protein binding domain belonging to the death domain superfamily (12). The structure of several PYDs has been determined, which revealed a bundle of 5- to 6-α-helices.…”

Section: Introductionmentioning

confidence: 99%

“…However, the precise function of most family members is still unknown (36–39). Besides NLRPs and ALRs, the PYD is also present in the inflammasome adaptor protein ASC, the regulatory PYD-only proteins (POPs) and Pyrin (Figure 1C) (12). Below, we will specifically discuss the mechanism of activation and function of NLRPs and ALRs, and how defects within these proteins are involved in immune-related disorders.…”

Section: Introductionmentioning

confidence: 99%

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An Update on PYRIN Domain-Containing Pattern Recognition Receptors: From Immunity to Pathology

2013

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Cytosolic pattern recognition receptors (PRRs) sense a wide range of endogenous danger-associated molecular patterns as well as exogenous pathogen-associated molecular patterns. In particular, Nod-like receptors containing a pyrin domain (PYD), called NLRPs, and AIM2-like receptors (ALRs) have been shown to play a critical role in host defense by facilitating clearance of pathogens and maintaining a healthy gut microflora. NLRPs and ALRs both encode a PYD, which is crucial for relaying signals that result in an efficient innate immune response through activation of several key innate immune signaling pathways. However, mutations in these PRRs have been linked to the development of auto-inflammatory and autoimmune diseases. In addition, they have been implicated in metabolic diseases. In this review, we summarize the function of PYD-containing NLRPs and ALRs and address their contribution to innate immunity, host defense, and immune-linked diseases.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An Update on PYRIN Domain-Containing Pattern Recognition Receptors: From Immunity to Pathology

2013

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“…Instead, the MYXV-encoded protein M013, which was first identified as a member of the PYRIN domain (PYD) superfamily, was shown to function as an intracellular inhibitor of inflammasome activation [33]. The cellular PYD-containing proteins mediate protein-protein interactions with components of signaling pathways involved in the regulation of apoptosis, NF-κB activation and pro-inflammatory cytokine production [34],[35]. Our initial study showed that a MYXV construct deleted for M013L (vMyxM013-KO) was significantly attenuated in host rabbits because of decreased virus dissemination and enhanced inflammatory responses at the tissue sites of virus infection [33].…”

Section: Introductionmentioning

confidence: 99%

Co-Regulation of NF-κB and Inflammasome-Mediated Inflammatory Responses by Myxoma Virus Pyrin Domain-Containing Protein M013

et al. 2009

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NF-κB and inflammasomes both play central roles in orchestrating anti-pathogen responses by rapidly inducing a variety of early-response cytokines and chemokines following infection. Myxoma virus (MYXV), a pathogenic poxvirus of rabbits, encodes a member of the cellular pyrin domain (PYD) superfamily, called M013. The viral M013 protein was previously shown to bind host ASC-1 protein and inhibit the cellular inflammasome complex that regulates the activation and secretion of caspase 1-regulated cytokines such as IL-1β and IL-18. Here, we report that human THP-1 monocytic cells infected with a MYXV construct deleted for the M013L gene (vMyxM013-KO), in stark contrast to the parental MYXV, rapidly induce high levels of secreted pro-inflammatory cytokines like TNF, IL-6, and MCP-1, all of which are regulated by NF-κB. The induction of these NF-κB regulated cytokines following infection with vMyxM013-KO was also confirmed in vivo using THP-1 derived xenografts in NOD-SCID mice. vMyxM013-KO virus infection specifically induced the rapid phosphorylation of IKK and degradation of IκBα, which was followed by nuclear translocation of NF-κB/p65. Even in the absence of virus infection, transiently expressed M013 protein alone inhibited cellular NF-κB-mediated reporter gene expression and nuclear translocation of NF-κB/p65. Using protein/protein interaction analysis, we show that M013 protein also binds directly with cellular NF-κB1, suggesting a direct physical and functional linkage between NF-κB1 and ASC-1. We further demonstrate that inhibition of the inflammasome with a caspase-1 inhibitor did not prevent the induction of NF-κB regulated cytokines following infection with vMyxM013-KO virus, but did block the activation of IL-1β. Thus, the poxviral M013 inhibitor exerts a dual immuno-subversive role in the simultaneous co-regulation of both the cellular inflammasome complex and NF-κB-mediated pro-inflammatory responses.

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“…FMF'e neden olan gen MEFV geni (Mediterranean Fever Gene) 16 numaralı kromozomda lokalize olup (16p13,3) 10 ekzona sahiptir ve 781 aminoasitlik pirin adı verilen bir proteini kodlar. Pirin, apopitotik ve inflamatuvar sinyal yolunda fonksiyonu olduğu düşünülen bir proteindir [6][7][8]. MEFV geninin ürünü olan pirin proteini interlökin 1β üretimini inhibe eder.…”

Section: Introductionunclassified

MEFV gen mutasyonlarının tüberküloza direnç ile olası ilişkisi

Yıldırım¹,

Yıldırım²,

Arslan³

et al. 2014

Cumhuriyet Med J

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ÖzetAmaç. Mycobacterium tuberculosis enfeksiyonu dünya üzerinde ciddi bir halk sağlığı sorunudur. T-helper 1 hücreleri tüberküloz patogenezinde önemli bir rol oynamaktadır. Ailesel Akdeniz Ateşi (FMF) hastaları ve taşıyıcılarında T-helper 1'in artmış aktivitesi söz konusudur. Bu çalışmayı, bağışıklık temelinde, MEFV gen mutasyonlarıyla tüberküloza karşı direnç arasında olası ilişkiyi değerlendirmek üzere yaptık. Anahtar sözcükler: FMF, tüberküloz, MEFV geni, mutasyon Abstract Aim. Mycobacterium tuberculosis infection is a critical public health problem all over the world. T-helper 1 cells play an important role in the pathogenesis of tuberculosis. There is an increased activity of T-helper 1 in Familial Mediterranean Fever (FMF) patients and carriers. Based on immunity, we undertaken this study to evaluate a possible association of MEFV gene mutations with resistance to tuberculosis. Method. This study was performed with 51 patients (23 females, 28 males) applied to Cumhuriyet University Medical Faculty Chest Diseases Department between 2007 and 2009 and diagnosed with tuberculosis by physical examination, microbiological and radiologic analysis and 57 controls (26 females, 31 males). In these groups, 12 common MEFV gene mutations were researched using revers hybridisation FMF Strip Assay (ViennaLab Labordiagnostika, Vienna, Austria) technique. Results. A significant difference was not detected between patient and control groups in terms of distribution of MEFV mutations (p>0.05). There were 22 MEFV gene mutations (43.1%) in patient group. Homozygous mutation was not detected in this group. All mutations in patient group were heterozygous. There was also no homozygous mutation in control group and total 29 (50.8%) heterozygous mutations were detected. Conclusion. Our results suggested that the mutation frequency of MEFV gene in tuberculosis patients was not significantly different from healthy population. FMF mutations may effect the survive of tuberculosis but not sicken.

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The PYRIN Domain in Signal Transduction

Cited by 24 publications

References 213 publications

An Update on PYRIN Domain-Containing Pattern Recognition Receptors: From Immunity to Pathology

An Update on PYRIN Domain-Containing Pattern Recognition Receptors: From Immunity to Pathology

Co-Regulation of NF-κB and Inflammasome-Mediated Inflammatory Responses by Myxoma Virus Pyrin Domain-Containing Protein M013

MEFV gen mutasyonlarının tüberküloza direnç ile olası ilişkisi

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