Nlrp4

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

CLR19.5; CT58; NALP4; NLR family; NLR family pyrin domain containing 4; PAN2; PYPAF4; pyrin domain containing 4; RNH2

Definition
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NLRPs (acronym for "NIGHT, LRR and PYD domains-containing protein) are, together with the NOD1 and NOD2 proteins, members of the NLR (Nod-like Receptor) protein family and play a major role in innate immunity as pathogen recognition receptors (PPRs). Like the NOD proteins, NLRPs are expressed exclusively cytoplasmically. All NLRPs (they all contain a pyrin domain) are encoded by a common gene family in humans. NLRPs are characterised by their ability to activate different inflammatory complexes.

Inflammasomes are differently composed cytosolic protein complexes, whereby the different NLRPs are of great importance for their functionality. Inflammasomes are predominantly found in immune cells such as dendritic cells and macrophages.

The activation of an inflammasome complex leads to the expression of different caspases, which convert inactive interleukin-1beta and interleukin-18 into their active form.

General information
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NIGHT, LRR and PYD domains-containing protein 4 (NALP4) is a cytosolic protein encoded in humans by the NLRP4 gene located on chromosome 19: 55.84. NLRP4 regulates the activation of type I interferons via double-stranded RNA or DNA by activating the serine/threonine kinase (TBK1), which in turn plays an essential role in the regulation of inflammatory responses to foreign agents.

NLRP4, NLRC4, NLRP3, and NLRP10 interact with Beclin1. Beclin-1 is a human protein that interacts with either BCL-2 or PI3k class III and plays a crucial role in the regulation of autophagocytic or apoptotic processes. Among these NLRs, NLRP4 shows a particularly strong affinity to Beclin1. Inhibition of NLRP4 activity results in activation of autophagocytic processes.

Literature
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  1. Charoenthongtrakul S et al (2012) The NLRP4-DTX4 axis: a key suppressor of TBK1 and innate antiviral signaling. Cell Mol Immunol 9:431-433.
  2. Cui J et al (2012) NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1 for degradation via the ubiquitin ligase DTX4. Nat Immunol 13:387-395.
  3. Jounai N et al (2011) NLRP4 negatively regulates autophagic processes through an association with beclin1. J Immunol 186:1646-1655.

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Last updated on: 29.10.2020