Artikel ; Online: The CLRX.1/NOD24 (NLRP2P) pseudogene codes a functional negative regulator of NF-κB, pyrin-only protein 4.
2014 Band 15, Heft 6, Seite(n) 392–403
Abstract: Pseudogenes are duplicated yet defunct copies of functional parent genes. However, some pseudogenes have gained or retained function. In this study, we consider a functional role for the NLRP2-related, higher primate-specific, processed pseudogene NLRP2P, ...
| Abstract | Pseudogenes are duplicated yet defunct copies of functional parent genes. However, some pseudogenes have gained or retained function. In this study, we consider a functional role for the NLRP2-related, higher primate-specific, processed pseudogene NLRP2P, which is closely related to Pyrin-only protein 2 (POP2/PYDC2), a regulator of nuclear factor-κB (NF-κB) and the inflammasome. The NLRP2P open-reading frame on chromosome X has features consistent with a processed pseudogene (retrotransposon), yet encodes a 45-amino-acid, Pyrin-domain-related protein. The open-reading frame of NLRP2P shares 80% identity with POP2 and is under purifying selection across Old World primates. Although widely expressed, NLRP2P messenger RNA is upregulated by lipopolysaccharide in human monocytic cells. Functionally, NLRP2P impairs NF-κB p65 transactivation by reducing activating phosphorylation of RelA/p65. Reminiscent of POP2, NLRP2P reduces production of the NF-κB-dependent cytokines tumor necrosis factor alpha and interleukin (IL)-6 following toll-like receptor stimulation. In contrast to POP2, NLRP2P fails to inhibit the ASC-dependent NLRP3 inflammasome. In addition, beyond regulating cytokine production, NLRP2P has a potential role in cell cycle regulation and cell death. Collectively, our findings suggest that NLRP2P is a resurrected processed pseudogene that regulates NF-κB RelA/p65 activity and thus represents the newest member of the POP family, POP4. |
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| Mesh-Begriff(e) | Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Apoptosis/genetics ; Apoptosis Regulatory Proteins ; Base Sequence ; Blotting, Western ; Cell Cycle/genetics ; Cell Line ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Gene Expression Regulation/drug effects ; HEK293 Cells ; HeLa Cells ; Humans ; Lipopolysaccharides/pharmacology ; Microscopy, Fluorescence ; Molecular Sequence Data ; Phosphorylation ; Pseudogenes/genetics ; RNA Interference ; Repressor Proteins/metabolism ; Retroelements/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Serine/metabolism ; Transcription Factor RelA/genetics ; Transcription Factor RelA/metabolism ; Tumor Necrosis Factor-alpha/pharmacology |
| Chemische Substanzen | Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; Lipopolysaccharides ; NLRP2 protein, human ; NLRP4 protein, human ; RELA protein, human ; Repressor Proteins ; Retroelements ; Transcription Factor RelA ; Tumor Necrosis Factor-alpha ; Serine (452VLY9402) |
| Sprache | Englisch |
| Erscheinungsdatum | 2014-05-29 |
| Erscheinungsland | England |
| Dokumenttyp | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2060566-3 |
| ISSN | 1476-5470 ; 1466-4879 |
| ISSN (online) | 1476-5470 |
| ISSN | 1466-4879 |
| DOI | 10.1038/gene.2014.30 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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