The Experts below are selected from a list of 1731 Experts worldwide ranked by ideXlab platform
Masaru Nonaka - One of the best experts on this subject based on the ideXlab platform.
-
Evolution of dimorphisms of the proteasome subunit beta type 8 gene (PSMB8) in basal ray-finned fish
Immunogenetics, 2014Co-Authors: Megumi Noro, Masaru NonakaAbstract:The proteasome subunit beta type 8 ( PSMB8 ) gene encodes a catalytic subunit of immunoproteasome that plays a central role in the processing of antigenic peptides presented by major histocompatibility complex class I molecules. The A- and F-type alleles defined by the 31st amino acid residue determining cleaving specificity have been identified from ray-finned fish, amphibia, and reptiles. These two types show extremely long-term trans-species polymorphism in Polypteriformes, Cypriniformes, and Salmoniformes, suggesting the presence of very ancient lineages termed A and F. To elucidate the evolution of the PSMB8 dimorphism in basal ray-finned fish, we analyzed Pantodon buchholzi (Osteoglossiformes), seven species of Anguilliformes, and Hypomesus nipponensis (Osmeriformes). Both A and F lineage sequences were identified from P. buchholzi and H. nipponensis , confirming that these two lineages have been conserved by basal ray-finned fish. However, both the A- and F-type alleles found in Anguilliformes species belonged to the F lineage irrespective of their types. This apparently suggests that the A lineage was lost in the common ancestor of Anguilliformes, and recovery of the A type within the F lineage occurred in Anguilliformes. The apparent loss of the F lineage and recovery of the F type within the A lineage have already been reported from tetrapods and higher teleosts. However, this is the first report on the reverse situation and reveals the dynamic evolution of the PSMB8 dimorphism.
-
Dimorphisms of the proteasome subunit beta type 8 gene (PSMB8) of ectothermic tetrapods originated in multiple independent evolutionary events
Immunogenetics, 2013Co-Authors: Ching-huei Huang, Naoko T. Fujito, Yuta Tanaka, Masaru NonakaAbstract:The proteasome subunit beta type 8 gene ( PSMB8 ) encodes one of the beta subunits of the immunoproteasome responsible for the generation of peptides presented by major histocompatibility complex class I molecules. Dimorphic alleles of the PSMB8 gene, termed A and F types, based on the deduced 31st amino acid residue of the mature protein have been reported from various vertebrates. Phylogenetic analysis revealed the presence of dichotomous ancient lineages, one comprising the F-type PSMB8 of basal ray-finned fishes, and the other comprising the A-type PSMB8 of these animals and both the F- and A-type PSMB8 of Xenopus and acanthopterygians, indicating that evolutionary history of the PSMB8 dimorphism was not straightforward. We analyzed the PSMB8 gene of five reptile and one amphibian species and found both the A and F types from all six. Phylogenetic analysis indicated that the PSMB8 F type was apparently regenerated from the PSMB8 A type at least five times independently during tetrapod evolution. Genomic typing of wild individuals of geckos and newts indicated that the frequencies of the A- and F-type alleles are not highly biased in these species. Phylogenetic analysis of each exon of the reptile PSMB8 gene suggested interallelic sequence homogenization as a possible evolutionary mechanism for the apparent recurrent regeneration of PSMB8 dimorphism in tetrapods. An extremely strong balancing selection acting on PSMB8 dimorphism was implicated in an unprecedented pattern of allele evolution.
-
Highly divergent dimorphic alleles of the proteasome subunit beta type-8 (PSMB8) gene of the bichir Polypterus senegalus: implication for evolution of the PSMB8 gene of jawed vertebrates
Immunogenetics, 2012Co-Authors: Naoko T. Fujito, Masaru NonakaAbstract:The proteasome subunit beta type-8 ( PSMB8 ) gene encodes a catalytic subunit of the immunoproteasome, which is involved in the generation of peptides presented by MHC class I molecules. To date, highly diverged dichotomous alleles of PSMB8 have been reported in Oryzias species (actinopterygian teleosts) and Xenopus species (sarcopterygian amphibians). These dimorphic alleles share a similar substitution (A/V^31F/Y) at the 31st position of the mature protein, which is most probably involved in formation of the S1 pocket. This substitution likely confers different cleavage specificities on the dimorphic PSMB8s. In addition, two paralogous PSMB8 genes possessing the A and F residues at the 31st position have been reported in sharks. Phylogenetic analysis indicated that the two types of PSMB8 of Oryzias , Xenopus , and sharks arose by independent evolutionary events. Here, we identified another pair of dimorphic alleles of PSMB8 , which have the A and F residues at the 31st position of the mature protein, from bichir, Polypterus senegalus , a basal actinopterygian. The sequences of the mature proteins-encoding region of the dimorphic alleles of bichir PSMB8 , the A and F types, showed only 72.7% and 77.5% identities at the nucleotide and the deduced amino acid levels, respectively. Their intronic sequences show almost no similarity, indicating that the dimorphic alleles of bichir PSMB8 have a very ancient origin. However, phylogenetic analysis showed that the dimorphisms of PSMB8 of bichir, Xenopus , and Oryzias arose by independent evolutionary events, suggesting the presence of a strong selective pressure for possessing the dimorphism.
-
Long-Lived Dichotomous Lineages of the Proteasome Subunit Beta Type 8 (PSMB8) Gene Surviving More than 500 Million Years as Alleles or Paralogs
Molecular biology and evolution, 2012Co-Authors: Kentaro Tsukamoto, Fumi Miura, Naoko T. Fujito, Goro Yoshizaki, Masaru NonakaAbstract:On an evolutionary time scale, polymorphic alleles are believed to have a short life, persisting at most tens of millions of years even under long-term balancing selection. Here, we report highly diverged trans-species dimorphism of the proteasome subunit beta type 8 (PSMB8) gene, which encodes a catalytic subunit of the immunoproteasome responsible for the generation of peptides presented by major histocompatibility complex (MHC) class I molecules, in lower teleosts including Cypriniformes (zebrafish and loach) and Salmoniformes (trout and salmon), whose last common ancestor dates to 300 Ma. Moreover, phylogenetic analyses indicated that these dimorphic alleles share lineages with two shark paralogous genes, suggesting that these two lineages have been maintained for more than 500 My either as alleles or as paralogs, and that conversion between alleles and paralogs has occurred at least once during vertebrate evolution. Two lineages termed PSMB8A and PSMB8F show an A(31)F substitution that would probably affect their cleaving specificity, and whereas the PSMB8A lineage has been retained by all analyzed jawed vertebrates, the PSMB8F lineage has been lost by most jawed vertebrates except for cartilaginous fish and basal teleosts. However, a possible functional equivalent of the PSMB8F lineage has been revived as alleles within the PSMB8A lineage at least twice during vertebrate evolution in the amphibian Xenopus and teleostean Oryzias species. Dynamic evolution of the PSMB8 polymorphism through long-term persistence, loss, and regaining of dimorphism and conversion between alleles and paralogs implies the presence of strong selective pressure for functional polymorphism of this gene.
-
Evolution of the Major Histocompatibility Complex: A Lesson from the Oryzias Species
Medaka, 2011Co-Authors: Masaru Nonaka, Kentaro TsukamotoAbstract:The genomic organization of the teleost major histocompatibility complex (MHC) shows a significant deviation from that of the “standard” MHC of the eutherian mammals in that the class IA genes are not linked to the class IIA and B genes. However, progress in the phylogenetic analysis of the jawed vertebrate MHC reveals that the “standard” mammalian MHC is also highly derived because the tight linkage between the class IA genes and the genes directly involved in the class I antigen processing/presentation process is disrupted. In the medaka MHC class I region, these genes form a tight and uninterrupted cluster, probably reflecting the ancestral genomic organization of the MHC. One of these genes, PSMB8 (proteasome subunit beta type 8), which is responsible for the generation of the peptides presented by the MHC class I molecules, shows a marked dimorphism in medaka. The same dimorphic alleles are present in other Oryzias species, indicating that they are under balancing selection and have been transmitted from species to species. Although the physiological or evolutionary meaning of this balancing selection is still to be clarified, similar dimorphisms of PSMB8 are widely recognized among non-eutherian vertebrates, suggesting that the presence of the PSMB8 dimorphism is associated with the tight linkage between the class IA genes and the genes directly involved in the class I antigen processing/presentation process.
Chengyi Sun - One of the best experts on this subject based on the ideXlab platform.
-
LncRNA PSMB8-AS1 contributes to pancreatic cancer progression via modulating miR-382-3p/STAT1/PD-L1 axis.
Journal of experimental & clinical cancer research : CR, 2020Co-Authors: Hao Zhang, Zhu Changhao, He Zhiwei, Shiyu Chen, Chengyi SunAbstract:Accumulating evidence demonstrates the essential role of long non-coding RNA (lncRNA) in various types of cancers, including pancreatic cancer. However, the functions and regulation mechanism of lncRNA PMSB8-AS1 in pancreatic cancer are largely unclear. Quantitative reverse transcription PCR (qRT-PCR) is used to examine the expression of PMSB8-AS1 in PC tissues and PC cell lines. The effect of PMSB8-AS1 on the proliferation of PC cells was detected using CCK8 assay, colony assay, and flow cytometry. The effect of PMSB8-AS1 on the migration and invasion of pancreatic cancer cells was detected using a wound-healing assay and transwell migration assay. Bioinformatic analysis, double luciferase reporting assay, western blot, and rescue experiments were used to detect the regulatory relationship between PMSB8-AS1, miR-382–3p, STAT1, and PD-L1. PMSB8-AS1 expression was upregulated in PC tissues and cell lines and positively associated with the worst survival in patients with PC. The in vitro and in vivo assays demonstrated that overexpression of PMSB8-AS1 significantly promoted pancreatic cancer cell proliferation, migration, and invasion, whereas knockdown of PMSB8-AS1 suppressed cell proliferation, migration, invasion, and EMT, and decreased apoptosis of PC cells. Besides, PMSB8-AS1 directly bound to miR-382–3p downregulated its expression. Besides, PMSB8-AS1 reversed the effect of miR-382–3p on the growth and metastasis of PC cells, which might be targeted on STAT1. Furthermore, STAT1 is the transcriptional factor that activates the expression of PD-L1. lncRNA PMSB8-AS1 promotes pancreatic cancer progression via STAT1 by sponging miR-382–3p involving regulation PD-L1.
-
lncrna PSMB8 as1 contributes to pancreatic cancer progression via modulating mir 382 3p stat1 pd l1 axis
Journal of Experimental & Clinical Cancer Research, 2020Co-Authors: Hao Zhang, Shiyu Chen, Changhao Zhu, Chengyi SunAbstract:Accumulating evidence demonstrates the essential role of long non-coding RNA (lncRNA) in various types of cancers, including pancreatic cancer. However, the functions and regulation mechanism of lncRNA PMSB8-AS1 in pancreatic cancer are largely unclear. Quantitative reverse transcription PCR (qRT-PCR) is used to examine the expression of PMSB8-AS1 in PC tissues and PC cell lines. The effect of PMSB8-AS1 on the proliferation of PC cells was detected using CCK8 assay, colony assay, and flow cytometry. The effect of PMSB8-AS1 on the migration and invasion of pancreatic cancer cells was detected using a wound-healing assay and transwell migration assay. Bioinformatic analysis, double luciferase reporting assay, western blot, and rescue experiments were used to detect the regulatory relationship between PMSB8-AS1, miR-382–3p, STAT1, and PD-L1. PMSB8-AS1 expression was upregulated in PC tissues and cell lines and positively associated with the worst survival in patients with PC. The in vitro and in vivo assays demonstrated that overexpression of PMSB8-AS1 significantly promoted pancreatic cancer cell proliferation, migration, and invasion, whereas knockdown of PMSB8-AS1 suppressed cell proliferation, migration, invasion, and EMT, and decreased apoptosis of PC cells. Besides, PMSB8-AS1 directly bound to miR-382–3p downregulated its expression. Besides, PMSB8-AS1 reversed the effect of miR-382–3p on the growth and metastasis of PC cells, which might be targeted on STAT1. Furthermore, STAT1 is the transcriptional factor that activates the expression of PD-L1. lncRNA PMSB8-AS1 promotes pancreatic cancer progression via STAT1 by sponging miR-382–3p involving regulation PD-L1.
Elke Krüger - One of the best experts on this subject based on the ideXlab platform.
-
contribution of the unfolded protein response upr to the pathogenesis of proteasome associated autoinflammatory syndromes praas
Frontiers in Immunology, 2019Co-Authors: Frederic Ebstein, Maria Cecilia Poli Harlowe, Maja Studenckaturski, Elke KrügerAbstract:Type I interferonopathies cover a phenotypically heterogeneous group of rare genetic diseases including the recently described proteasome-associated autoinflammatory syndromes (PRAAS). By definition, PRAAS are caused by inherited and/or de novo loss-of-function mutations in genes encoding proteasome subunits such as PSMB8, PSMB9, PSMB7, PSMA3, or proteasome assembly factors including POMP and PSMG2, respectively. Disruption of any of these subunits results in perturbed intracellular protein homeostasis including accumulation of ubiquitinated proteins which is accompanied by a type I interferon (IFN) signature. The observation that, similarly to pathogens, proteasome dysfunctions are potent type I IFN inducers is quite unexpected and, up to now, the underlying molecular mechanisms of this process remain largely unknown. One promising candidate for triggering type I IFN under sterile conditions is the unfolded protein response (UPR) which is typically initiated in response to an accumulation of unfolded and/or misfolded proteins in the endoplasmic reticulum (ER) (also referred to as ER stress). The recent observation that the UPR is engaged in subjects carrying POMP mutations strongly suggests its possible implication in the cause-and-effect relationship between proteasome impairment and interferonopathy onset. The purpose of this present review is therefore to discuss the possible role of the UPR in the pathogenesis of PRAAS. We will particularly focus on pathways initiated by the four ER-membrane proteins ATF6, PERK, IRE1-α, and TCF11/Nrf1 which undergo activation under proteasome inhibition. An overview of the current understanding of the mechanisms and potential cross-talk between the UPR and inflammatory signaling casacades is provided to convey a more integrated picture of the pathophysiology of PRAAS and shed light on potential biomarkers and therapeutic targets.
Maria Cecilia Poli Harlowe - One of the best experts on this subject based on the ideXlab platform.
-
contribution of the unfolded protein response upr to the pathogenesis of proteasome associated autoinflammatory syndromes praas
Frontiers in Immunology, 2019Co-Authors: Frederic Ebstein, Maria Cecilia Poli Harlowe, Maja Studenckaturski, Elke KrügerAbstract:Type I interferonopathies cover a phenotypically heterogeneous group of rare genetic diseases including the recently described proteasome-associated autoinflammatory syndromes (PRAAS). By definition, PRAAS are caused by inherited and/or de novo loss-of-function mutations in genes encoding proteasome subunits such as PSMB8, PSMB9, PSMB7, PSMA3, or proteasome assembly factors including POMP and PSMG2, respectively. Disruption of any of these subunits results in perturbed intracellular protein homeostasis including accumulation of ubiquitinated proteins which is accompanied by a type I interferon (IFN) signature. The observation that, similarly to pathogens, proteasome dysfunctions are potent type I IFN inducers is quite unexpected and, up to now, the underlying molecular mechanisms of this process remain largely unknown. One promising candidate for triggering type I IFN under sterile conditions is the unfolded protein response (UPR) which is typically initiated in response to an accumulation of unfolded and/or misfolded proteins in the endoplasmic reticulum (ER) (also referred to as ER stress). The recent observation that the UPR is engaged in subjects carrying POMP mutations strongly suggests its possible implication in the cause-and-effect relationship between proteasome impairment and interferonopathy onset. The purpose of this present review is therefore to discuss the possible role of the UPR in the pathogenesis of PRAAS. We will particularly focus on pathways initiated by the four ER-membrane proteins ATF6, PERK, IRE1-α, and TCF11/Nrf1 which undergo activation under proteasome inhibition. An overview of the current understanding of the mechanisms and potential cross-talk between the UPR and inflammatory signaling casacades is provided to convey a more integrated picture of the pathophysiology of PRAAS and shed light on potential biomarkers and therapeutic targets.
Kentaro Tsukamoto - One of the best experts on this subject based on the ideXlab platform.
-
Long-Lived Dichotomous Lineages of the Proteasome Subunit Beta Type 8 (PSMB8) Gene Surviving More than 500 Million Years as Alleles or Paralogs
Molecular biology and evolution, 2012Co-Authors: Kentaro Tsukamoto, Fumi Miura, Naoko T. Fujito, Goro Yoshizaki, Masaru NonakaAbstract:On an evolutionary time scale, polymorphic alleles are believed to have a short life, persisting at most tens of millions of years even under long-term balancing selection. Here, we report highly diverged trans-species dimorphism of the proteasome subunit beta type 8 (PSMB8) gene, which encodes a catalytic subunit of the immunoproteasome responsible for the generation of peptides presented by major histocompatibility complex (MHC) class I molecules, in lower teleosts including Cypriniformes (zebrafish and loach) and Salmoniformes (trout and salmon), whose last common ancestor dates to 300 Ma. Moreover, phylogenetic analyses indicated that these dimorphic alleles share lineages with two shark paralogous genes, suggesting that these two lineages have been maintained for more than 500 My either as alleles or as paralogs, and that conversion between alleles and paralogs has occurred at least once during vertebrate evolution. Two lineages termed PSMB8A and PSMB8F show an A(31)F substitution that would probably affect their cleaving specificity, and whereas the PSMB8A lineage has been retained by all analyzed jawed vertebrates, the PSMB8F lineage has been lost by most jawed vertebrates except for cartilaginous fish and basal teleosts. However, a possible functional equivalent of the PSMB8F lineage has been revived as alleles within the PSMB8A lineage at least twice during vertebrate evolution in the amphibian Xenopus and teleostean Oryzias species. Dynamic evolution of the PSMB8 polymorphism through long-term persistence, loss, and regaining of dimorphism and conversion between alleles and paralogs implies the presence of strong selective pressure for functional polymorphism of this gene.
-
Evolution of the Major Histocompatibility Complex: A Lesson from the Oryzias Species
Medaka, 2011Co-Authors: Masaru Nonaka, Kentaro TsukamotoAbstract:The genomic organization of the teleost major histocompatibility complex (MHC) shows a significant deviation from that of the “standard” MHC of the eutherian mammals in that the class IA genes are not linked to the class IIA and B genes. However, progress in the phylogenetic analysis of the jawed vertebrate MHC reveals that the “standard” mammalian MHC is also highly derived because the tight linkage between the class IA genes and the genes directly involved in the class I antigen processing/presentation process is disrupted. In the medaka MHC class I region, these genes form a tight and uninterrupted cluster, probably reflecting the ancestral genomic organization of the MHC. One of these genes, PSMB8 (proteasome subunit beta type 8), which is responsible for the generation of the peptides presented by the MHC class I molecules, shows a marked dimorphism in medaka. The same dimorphic alleles are present in other Oryzias species, indicating that they are under balancing selection and have been transmitted from species to species. Although the physiological or evolutionary meaning of this balancing selection is still to be clarified, similar dimorphisms of PSMB8 are widely recognized among non-eutherian vertebrates, suggesting that the presence of the PSMB8 dimorphism is associated with the tight linkage between the class IA genes and the genes directly involved in the class I antigen processing/presentation process.
-
Transspecies dimorphic allelic lineages of the proteasome subunit β-type 8 gene (PSMB8) in the teleost genus Oryzias
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Fumi Miura, Ratnesh Bhai Mehta, Kentaro Tsukamoto, Kiyoshi Naruse, Wichian Magtoon, Masaru NonakaAbstract:The proteasome subunit β-type 8 (PSMB8) gene in the jawed vertebrate MHC genomic region encodes a catalytic subunit of the immunoproteasome involved in the generation of peptides to be presented by the MHC class I molecules. A teleost, the medaka (Oryzias latipes), has highly diverged dimorphic allelic lineages of the PSMB8 gene with only about 80% amino acid identity, termed "PSMB8d" and "PSMB8N," which have been retained by most wild populations analyzed. To elucidate the evolutionary origin of these two allelic lineages, seven species of the genus Oryzias were analyzed for their PSMB8 allelic sequences using a large number of individuals from wild populations. All the PSMB8 alleles of these species were classified into one of these two allelic lineages based on their nucleotide sequences of exons and introns, indicating that the Oryzias PSMB8 gene has a truly dichotomous allelic lineage. Retention of both allelic lineages was confirmed except for one species. The PSMB8d lineage showed a higher frequency than the PSMB8N lineage in all seven species. The two allelic lineages showed curious substitutions at the 31st and 53rd residues of the mature peptide, probably involved in formation of the S1 pocket, suggesting that these allelic lineages show a functional difference in cleavage specificity. These results indicate that the PSMB8 dimorphism was established before speciation within the genus Oryzias and has been maintained for more than 30-60 million years under a strict and asymmetric balancing selection through several speciation events.
-
Dichotomous haplotypic lineages of the immunoproteasome subunit genes, PSMB8 and PSMB10, in the MHC class I region of a teleost medaka, Oryzias latipes
Molecular biology and evolution, 2009Co-Authors: Kentaro Tsukamoto, Mitsuru Sakaizumi, Masayoshi Hata, Yuji Sawara, Jaeyoung Eah, Chang Bae Kim, Masaru NonakaAbstract:Sequence comparison of the medaka, Oryzias latipes, major histocompatibility complex (MHC) class I region between two inbred strains, the HNI (derived from the Northern Population) and the Hd-rR (from the Southern Population), revealed a approximately 100 kb highly divergent segment encompassing two MHC class IA genes, Orla-UAA and Orla-UBA, and two immunoproteasome beta subunit genes, PSMB8 and PSMB10. To elucidate the genetic diversity of this region, we analyzed polymorphisms of the PSMB8 and PSMB10 genes using wild populations of medaka from three genetically different groups: the Northern Population, the Southern Population, and the China-West Korean Population. A total of 1,245 specimens from 10 localities were analyzed, and all the PSMB8 and PSMB10 alleles were classified into the N (fixed in the HNI strain) or the d (fixed in the Hd-rR strain) lineage. Polymerase chain reaction analysis of the region from PSMB8 to PSMB10 indicated that the two allelic lineages of these genes are segregating together constituting dichotomous haplotypic lineages. Both haplotypic lineages were identified in all three groups, although the frequency of d haplotypic lineage (73-100%) was much higher than that of N haplotypic lineage (0-27%) in all analyzed populations. The two allelic lineages of the PSMB8 gene showed curious substitutions at the 31st and 53rd residues of the mature peptide, which are likely involved in formation of the S1 pocket, suggesting that these alleles have a functional difference in cleavage specificity. These results indicate that the two medaka MHC haplotypic lineages encompassing the PSMB8 and PSMB10 genes are maintained in wild populations by a balancing selection.
