Comprehensive analysis of the association between UBAC2 polymorphisms and Behçet’s disease in a Japanese population

Yamazoe, Kyoko; Meguro, Akira; Takeuchi, Masaki; Shibuya, Etsuko; Ohno, Shigeaki; Mizuki, Nobuhisa

doi:10.1038/s41598-017-00877-3

Cited by 21 publications

(17 citation statements)

References 29 publications

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“…The ubiquitin-associated domain-containing protein 2(UBAC2) gene is located on chromosome 13q32.3 and encodes UBAC2 protein that is a highly conserved protein in different species 6 , 7 . It was reported that the polymorphism of UBAC2 gene was related to Behcet’s disease and UBAC2 gene was the risk allele of Behcet’s disease 8 – 11 . The upregulation of UBAC2 expression can promote the progress of Behcet’s disease 11 .…”

Section: Introductionmentioning

confidence: 99%

“…It was reported that the polymorphism of UBAC2 gene was related to Behcet’s disease and UBAC2 gene was the risk allele of Behcet’s disease 8 – 11 . The upregulation of UBAC2 expression can promote the progress of Behcet’s disease 11 . Recently, a growing body of evidences demonstrated that UBAC2 was also closely related to the occurrence and development of malignant tumors, such as skin cancer and BC 12 , 13 .…”

Section: Introductionmentioning

confidence: 99%

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UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis

Zhao

Zhou

et al. 2020

Cell Death Dis

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Emerging evidences have demonstrated that ubiquitin-associated domain-containing protein 2 (UBAC2) is closely related to the occurrence and development of malignant tumors. However, the functions and underlying molecular mechanisms of UBAC2 in bladder cancer (BC) development have not been defined. In this study, we found that both UBAC2 mRNA and protein levels were upregulated in BC tissues and cell lines, and knockdown of UBAC2 inhibited BC cells proliferation both in vitro and in vivo. Meanwhile, Kaplan–Meier survival plots of 406 BC cases from TCGA database showed that higher expression of UBAC2 in BC patients was associated with lower survival rate. Mechanistic studies revealed that knockdown of UBAC2 increased the expression of p27 by posttranscriptional regulation. Our previous study indicated that circular RNA BCRC-3 (BCRC-3) promoted the expression of p27 through interacting with miR-182-5p, and reversed miR-182-5p-induced inhibition of p27 3′UTR activity. In the present study, we found that UBAC2 could bind to BCRC-3, and subsequently affected the interaction of BCRC-3 with miR-182-5p to inhibit the expression of p27. Furthermore, knockdown of BCRC-3 partly reversed the upregulation of p27 expression induced by knockdown of UBAC2. Our findings highlight a novel mechanism of UBAC2 in regulating p27 through affecting the function of BCRC-3, and provide a research basis for the diagnostic and therapeutic application of BC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis

Zhao

Zhou

et al. 2020

Cell Death Dis

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“…Studies in mammalian cells have shown that the UBAC2 in the ER also plays a role in cellular energy homeostasis through controlling cytoplasmic lipid droplet turnover (Suzuki et al, 2012;Wang and Lee, 2012;Olzmann et al, 2013). Polymorphisms in the UBAC2 gene have also been associated with Behcet's disease, a systemic inflammatory disorder in human (Sawalha et al, 2011;Hou et al, 2012;Yamazoe et al, 2017). Given the diverse and complex roles of UBAC2 proteins, it is likely that the evolutionarily conserved ER proteins participate in a range of cellular and molecular processes through distinct mechanisms and pathways.…”

Section: Discussionmentioning

confidence: 99%

Arabidopsis Endoplasmic Reticulum-Localized UBAC2 Proteins Interact with PAMP-INDUCED COILED-COIL to Regulate Pathogen-Induced Callose Deposition and Plant Immunity

Wang

et al. 2019

Plant Cell

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Pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) is initiated upon PAMP recognition by pattern recognition receptors (PRR). PTI signals are transmitted through activation of mitogen-activated protein kinases (MAPKs), inducing signaling and defense processes such as reactive oxygen species (ROS) production and callose deposition. Here, we examine mutants for two Arabidopsis thaliana genes encoding homologs of UBIQUITIN-ASSOCIATED DOMAIN-CONTAINING PROTEIN 2 (UBAC2), a conserved endoplasmic reticulum (ER) protein implicated in ER protein quality control. The ubac2 mutants were hypersusceptible to a type III secretion-deficient strain of the bacterial pathogen Pseudomonas syringae, indicating a PTI defect. The ubac2 mutants showed normal PRR biogenesis, MAPK activation, ROS burst, and PTI-associated gene expression. Pathogen-and PAMP-induced callose deposition, however, was compromised in ubac2 mutants. UBAC2 proteins interact with the plant-specific long coiled-coil protein PAMP-INDUCED COILED COIL (PICC), and picc mutants were compromised in callose deposition and PTI. Compromised callose deposition in the ubac2 and picc mutants was associated with reduced accumulation of the POWDERY MILDEW RESISTANT 4 (PMR4) callose synthase, which is responsible for pathogen-induced callose synthesis. Constitutive overexpression of PMR4 restored pathogen-induced callose synthesis and PTI in the ubac2 and picc mutants. These results uncover an ER pathway involving the conserved UBAC2 and plant-specific PICC proteins that specifically regulate pathogen-induced callose deposition in plant innate immunity.

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“…Limited studies suggest that it may function in protein localization in the endoplasmic reticulum [127]. The association of the UBAC2 gene with BD was found in Turkish, Chinese, Italian, and Japanese populations [128][129][130][131]. Functionally, the presence of BD-risk rs9517723 allele was correlated with an increased expression of the UBAC2 gene.…”

Section: Ubac2mentioning

confidence: 99%

Genetics of Behçet’s Disease

Zhou¹,

Deng²

2020

Different Aspects of Behçet's Disease

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Behçet's disease (BD) is a chronic refractory multi-system autoimmune disorder with a strong genetic component. Like many other human complex diseases, multiple genes with polymorphisms have been associated with BD. These genes encode proteins involved mainly in immune regulation and inflammation and some in transcriptional activation and post-translational modification. Understanding the genetic association of these genes with BD may provide insight into the pathogenesis and for development of new, targeted therapies for this human complex disease.

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Comprehensive analysis of the association between UBAC2 polymorphisms and Behçet’s disease in a Japanese population

Cited by 21 publications

References 29 publications

UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis

UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis

Arabidopsis Endoplasmic Reticulum-Localized UBAC2 Proteins Interact with PAMP-INDUCED COILED-COIL to Regulate Pathogen-Induced Callose Deposition and Plant Immunity

Genetics of Behçet’s Disease

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