Genetic variations in the <i>PSMA6</i> and <i>PSMC6</i> proteasome genes are associated with multiple sclerosis and response to interferon‑β therapy in Latvians

Paramonova, Natalia; Kalnina, Jolanta; Dokane, Kristine; Dišlere, Kristīne; Trapiņa, Ilva; Sjakste, Tatjana; Sjakste, Nikolajs

doi:10.3892/etm.2021.9909

Cited by 3 publications

(1 citation statement)

References 70 publications

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“…The localization of Ub conjugates in patients with MS might indicate UPS deterioration. Although the UPS participates in the pathogenesis of MS, details of the relationship between UPS and MS remain unknown [ 67 ]. Increased functional repression of the UPS and of interferon beta-1b (IFN-β1b) levels results in the development of MS. A better understanding of the molecular network of the UPS should provide more insight into the pathogenesis of MS. Myeloid leukemia 1 (MCL-1) is regulated by the UPS and is upregulated in MS [ 68 ].…”

Section: Therapeutic Targets In Upsmentioning

confidence: 99%

Modulating the Ubiquitin–Proteasome System: A Therapeutic Strategy for Autoimmune Diseases

Yadav

Lee

Puranik

et al. 2022

Cells

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Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease associated with the central nervous system (CNS). Autoimmunity is caused by an abnormal immune response to self-antigens, which results in chronic inflammation and tissue death. Ubiquitination is a post-translational modification in which ubiquitin molecules are attached to proteins by ubiquitinating enzymes, and then the modified proteins are degraded by the proteasome system. In addition to regulating proteasomal degradation of proteins, ubiquitination also regulates other cellular functions that are independent of proteasomal degradation. It plays a vital role in intracellular protein turnover and immune signaling and responses. The ubiquitin–proteasome system (UPS) is primarily responsible for the nonlysosomal proteolysis of intracellular proteins. The 26S proteasome is a multicatalytic adenosine-triphosphate-dependent protease that recognizes ubiquitin covalently attached to particular proteins and targets them for degradation. Damaged, oxidized, or misfolded proteins, as well as regulatory proteins that govern many essential cellular functions, are removed by this degradation pathway. When this system is affected, cellular homeostasis is altered, resulting in the induction of a range of diseases. This review discusses the biochemistry and molecular biology of the UPS, including its role in the development of MS and proteinopathies. Potential therapies and targets involving the UPS are also addressed.

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Section: Therapeutic Targets In Upsmentioning

confidence: 99%

Modulating the Ubiquitin–Proteasome System: A Therapeutic Strategy for Autoimmune Diseases

Yadav

Lee

Puranik

et al. 2022

Cells

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The Genetic Diversity of Proteasome Genes in the T1DM Polish Population

Strózik

Jędrychowska-Dańska

Zamerska

et al. 2023

CDR

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Background: Autoimmune metabolic diseases generate numerous healthy and social problems. The possible association of SNPs in the ubiquitin-proteasome system (UPS) with human pathology is under intensive study. Objective: In the present study, the genetic variations in PSMB5 (rs11543947), PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071) UPS gene cluster was investigated in type 1 diabetes and healthy donors in the Polish population. Methods: The study comprised 105 patients with type 1 diabetes mellitus (T1DM) and 214 controls. All were genotyped by PCR and restriction digestion analysis or Sanger sequencing. Results: Rs1048990 and rs2348071 were found to be neutral to T1DM (p-value: 0.499 and 0.656, respectively). According to the multiple loci genotype (MLG) analysis, the major homozygote of the tested polymorphisms had a protective effect. The most common MLG in the T1DM group was characterised by simultaneous risk factors at rs11543947, rs2277460, rs2295826 and rs2295827 (p-value: <0.0001 vs. MGL1). Multiple locus haplotype analysis revealed a similar dependence, with common alleles at all tested loci demonstrating a protective effect, and the rare alleles increasing T1DM risk (p-value: <0.0001 vs. MLH1). Conclusion: Our study suggests that the proteasome gene polymorphisms rs11543947, rs2277460, rs2295826, and rs2295827 could be potential markers for T1DM susceptibility in the Polish population.

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Analytical screening of polymorphic variants of 20S proteasome genes when planning a study of pathogenetic effects of modification of NFKB1 post-translational processing

Meyer

Ulyanova

Imekina

et al. 2023

Fundamentalʹnaâ i kliničeskaâ medicina

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Aim. Formation of polymorphic variants panel of the proteasome genes 20S, potentially significant for the study as balance modifier factors of p105/p50 NFKB1.Materials and methods. Determination of genes that encode proteins of the multisubunit proteasome complex prospective for research purposes, was carried out on the basis of information retrieved from eLIBRARY and PubMed. The source of information for the formation of polymorphic variants panel of genes (SNP, single nucleotide polymorphism) was the Ensembl genomic browser, http://www.ensembl.org. The structure of genes is described by the NCBI (databases Gene, http:// www.ncbi.nlm.nih.gov/gene). The panel was filled with the minor allelic frequency in the population (MAF), the localization of SNP in the gene structure and the availability of data on the relationship with multifactorial diseases and other effects in mind. To calculate the genetic distances between populations, we used the methord of comparing the populations by frequencies of polymorphic marker alleles proposed by Ney, the obtained matrices are illustrated by the method of multidimensional scaling in space using Statistica v.8.0.Results. Discussion of the algorithm and results of analytical screening of polymorphic variants of 14 genes (PSMA1-PSMA7, PSMB1–PSMB7) encoding proteasome subunits 20S. The characteristics of the SNP panel are given, compiled with the selection criteria taken into account. According to the data on the frequencies of polymorphic gene variants, the features of global and European population gene pools (283 SNP), as well as samples from Russian populations (20 SNP) are analyzed. Based on the results of the analysis of information on the associations of selected SNPs with various diseases, a panel (42 SNPs) of 20S proteasome genes was formed, potentially significant for the study as factors modifying the p105/p50 NFKB1 balance.Conclusion. Annotation of the formed panel of SNP genes of the 20S proteasome with MAF>0.1 indicates the potential role of polymorphism in the pathogenesis of diseases of various profiles. This may be of research interest to the formed panel in context of implementation of traditional approaches – the search for candidate genes based on the analysis of associations with diseases, as well as the analysis of the influence of SNP on the level of genetic expression, synthesis of gene products, NFKB1 processing and p105/p50 balance in silico and on model objects.

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Genetic variations in the PSMA6 and PSMC6 proteasome genes are associated with multiple sclerosis and response to interferon‑β therapy in Latvians

Cited by 3 publications

References 70 publications

Modulating the Ubiquitin–Proteasome System: A Therapeutic Strategy for Autoimmune Diseases

Modulating the Ubiquitin–Proteasome System: A Therapeutic Strategy for Autoimmune Diseases

The Genetic Diversity of Proteasome Genes in the T1DM Polish Population

Analytical screening of polymorphic variants of 20S proteasome genes when planning a study of pathogenetic effects of modification of NFKB1 post-translational processing

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