Association of <i>PELI1</i> polymorphisms in systemic lupus erythematosus susceptibility in a Chinese population

Chen, F-R; Zhai, Z-F; Shi, X-W; Feng, Lei; Zhong, B-Y; Wj, Yan; Wang, H; Chen, Y; You, Yi; Luo, Na; Zhang, D-M; Fei, Hao

doi:10.1177/0961203315571463

Cited by 7 publications

(6 citation statements)

References 45 publications

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“…Published study demonstrated that PELI1 polymorphisms is genetically associated with SLE susceptibility in Chinese population 37 , we then collected PBMCs from healthy donors (HD) and SLE patients to investigate the potential role of PELI1 in regulating B cell-mediated immune response and SLE pathogenesis. Under healthy conditions, there are very few antibody-producing plasma cells detected in HD PBMCs.…”

Section: Resultsmentioning

confidence: 99%

Peli1 negatively regulates noncanonical NF-κB signaling to restrain systemic lupus erythematosus

et al. 2018

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Systemic lupus erythematosus (SLE) is characterized by uncontrolled secretion of autoantibodies by plasma cells. Although the functional importance of plasma cells and autoantibodies in SLE has been well established, the underlying molecular mechanisms of controlling autoantibody production remain poorly understood. Here we show that Peli1 has a B cell-intrinsic function to protect against lupus-like autoimmunity in mice. Peli1 deficiency in B cells induces autoantibody production via noncanonical NF-κB signaling. Mechanically, Peli1 functions as an E3 ligase to associate with NF-κB inducing kinase (NIK) and mediates NIK Lys48 ubiquitination and degradation. Overexpression of Peli1 inhibits noncanonical NF-κB activation and alleviates lupus-like disease. In humans, PELI1 levels negatively correlate with disease severity in SLE patients. Our findings establish Peli1 as a negative regulator of the noncanonical NF-κB pathway in the context of restraining the pathogenesis of lupus-like disease.

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Section: Resultsmentioning

confidence: 99%

Peli1 negatively regulates noncanonical NF-κB signaling to restrain systemic lupus erythematosus

et al. 2018

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“…Elevated levels of Pellino1 and Pellino2 have been recorded in asthmatics , children with protracted bacterial bronchitis , and in transplant patients with acute kidney rejection . Furthermore, polymorphisms in the PELI1 locus, that encodes Pellino1, associate with vasculitis in young children and with increased susceptibility to systemic lupus erythematosus in a Chinese population . While the latter studies are restricted to interpreting association of Pellino genes and proteins with disease, a number of disease models have recently highlighted that Pellino proteins may play key roles in various pathogenic processes.…”

Section: Pellino Proteins As Regulators and Mediators Of Diseasementioning

confidence: 99%

Molecular and physiological roles of Pellino E3 ubiquitin ligases in immunity

Humphries

Moynagh

2015

Immunological Reviews

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The sensing of foreign agents by the innate and adaptive immune system triggers complex signal transduction cascades that culminate in expression of gene patterns that facilitate host protection from the invading agent. Post-translational modification of intracellular signaling proteins in these pathways is a key regulatory mechanism with ubiquitination being one of the important processes that controls levels and activities of signaling molecules. E3 ubiquitin ligases are the determining enzymes in dictating the ubiquitination status of individual proteins. Among these hundred E3 ubiquitin ligases are a family of Pellino proteins that are emerging to be important players in immunity and beyond. Herein, we review the roles of the Pellino E3 ubiquitin ligases in innate and adaptive immunity. We discuss their early discovery and characterization and how this has been aided by the highly conserved nature of innate immune signaling across evolution. We describe the molecular roles of Pellino proteins in immune signaling with particular emphasis on their involvement in pathogen recognition receptor (PRR) signaling. The growing appreciation of the importance of Pellino proteins in a wide range of immune-mediated diseases are also evaluated.

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“…The rs2607420 was related to risk of congenital megacolon in a Korean population (Kim et al ., 2017). In addition, rs329497 in PELI1 had a strong relationship with an autoimmune disease in a Chinese population (Chen et al ., 2015). In the present study, we genotyped these SNPs in a case-control cohort and evaluated their associations with CRC risk.…”

Section: Introductionmentioning

confidence: 99%

Immune-related genes STIM1, ITPKC and PELI1 polymorphisms are associated with risk of colorectal cancer

Zhu

Zheng

et al. 2021

European Journal of Cancer Prevention

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Objectives STIM1, ITPKC and PELI1 are all immunerelated genes that take part in the T cell activation, toll-like receptor and IL1 receptor pathways. The goal of this study was to evaluate the associations between STIM1, ITPKC and PELI1 polymorphisms and colorectal cancer (CRC) risk.Methods Six single nucleotide polymorphisms (SNPs) in STIM1, ITPKC and PELI1 were genotyped using a MassARRAY platform in a discovery cohort including 480 CRC cases and 480 healthy individuals and validated in a replication cohort including 505 CRC cases and 510 controls. ResultsThe minor alleles of rs3794050, rs3750996 and rs2607420 were associated with an increased CRC risk (P < 0.05). In contrast, the minor allele of rs329497 was correlated with reduced disease risk (P = 0.025). Genetic model analysis showed that rs3794050 was related to an increased risk of disease in recessive and log-additive models (P < 0.05); rs3750996 had a strong correlation with CRC risk under all genetic models (P < 0.02); rs2607420 was correlated with an increased risk of disease in dominant and log-additive models (P < 0.01); whereas the protective effect of rs329497 on CRC risk was observed in dominant and log-additive models (P < 0.05). Finally, the association between the above SNPs and CRC risk was validated in a replication cohort (P < 0.05).Conclusions Our results could be helpful for the early screening of individuals with high CRC risk. European

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Association of PELI1 polymorphisms in systemic lupus erythematosus susceptibility in a Chinese population

Abstract: In the Chinese Han population, PELI1 SNPs may be associated with SLE susceptibility.

Cited by 7 publications

References 45 publications

Peli1 negatively regulates noncanonical NF-κB signaling to restrain systemic lupus erythematosus

Peli1 negatively regulates noncanonical NF-κB signaling to restrain systemic lupus erythematosus

Molecular and physiological roles of Pellino E3 ubiquitin ligases in immunity

Immune-related genes STIM1, ITPKC and PELI1 polymorphisms are associated with risk of colorectal cancer

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