Korea Research Institute of Bioscience and Biotechnology
KRIBB Open Access RepositoryNot a member yet
15834 research outputs found
Sort by
Sjogren syndrome antigen B regulates LIN28-let-7 axis in Caenorhabditis elegans and human
No full textLIN28 protein and let-7 family micro RNAs (miRNAs) that are an evolutionarily conserved from nematodes to humans are the important regulators of developmental timing by dynamically interacting with each other. However, regulators of LIN28 remain largely elusive. Here, we show the evidences that Sjogren Syndrome antigen B (SSB) protein associates and cooperates with LIN28A and LIN28B, mammalian orthologues of Caenorhabditis elegans lin-28, proteins in the nucleus. Knockdown of SSB in HEK293 cell line resulted in the decrease of the amount of LIN28B mRNAs and proteins, and the increase of the level of mature let-7 miRNAs. Furthermore, RNA interference of ssb-1 gene, a worm SSB orthologue, was sufficient to cause a heterochronic defect in seam cells of C. elegans, recapitulating the phenotype of lin-28 downregulation. Collectively, we suggest that SSB is an important regulator for the LIN28-let-7 axis.
Complete genome of Polaromonas vacuolata KCTC 22033T isolated from beneath Antarctic Sea ice
No full textPolaromonas vacuolata KCTC 22033T is an obligate aerobic, Gram-negative, psychrophilic and rod-shaped bacterium isolated from beneath the sea ice off the coast of the Palmer Peninsula, Anvers Islands, Antarctica. P. vacuolata is the type species of Polaromonas genus and the first example of gas vacuolate Betaproteobacteria isolated from marine habitats. Here, we report a complete genome of P. vacuolata KCTC 22033T, which consists of 3,837,686 bp (G + C content of 52.07%) with a single chromosome, 3461 protein-coding genes, 56 tRNAs and 6 rRNA operons. Genomic analysis revealed the presence of genes involved in bacterial adaptation under saline conditions, cold adaptation via the production of gas vesicles and cell adhesion proteins, and a photoheterotrophic lifestyle when challenged by starvation. Intriguingly, several of these genes were likely acquired from species outside the Polaromonas genus. The genomic information therefore describes the unique evolution and adaptation of P. vacuolata to its extraordinary habitat, i.e., beneath the Antarctic sea ice.
A pipecolic acid-rich branched cyclic depsipeptide ulleungamide C from a Streptomyces species induces G0/G1 cell cycle arrest in promyelocytic leukemia cells
No full textIn this study, screening by LC-MS and cytotoxicity-guided isolation led to the identification of ulleungamide C (1), a previously unknown pipecolic acid-rich branched cyclic depsipeptide, from a soil actinobacterium Streptomyces sp. KCB13F003. The structure of 1 was determined by interpretation of spectroscopic and spectrometric data from 1D and 2D NMR and HRESIMS experiments. Antiproliferative assays using mammalian cancerous cells revealed that 1 inhibits the proliferation of HL-60 human promyelocytic leukemia cells. Cell cycle analysis showed an increased accumulation of cells in the G0/G1 phase after treatment with 1. Results of immunoblotting assays revealed that 1 reduced the expression levels of cyclin-dependent kinase 4 (CDK4), CDK6, retinoblastoma protein (Rb), and phosphorylated Rb, whereas it induced cyclin-dependent kinase inhibitor 1B (p27/Kip1) expression.
P62-induced cancer-associated fibroblast activation via the Nrf2-ATF6 pathway promotes lung tumorigenesis
No full textCancer-associated fibroblasts (CAFs) are important in tumor progression. The autophagy adaptor protein, p62/SQSTM1/Sequestosome-1, is up-regulated in tumors, but down-regulated in CAFs in the early stages of lung adenocarcinoma. We investigated whether p62-induced autophagy might control CAF activation. Under CAF-inducing conditions, like hypoxia or cancer cell co-cultures, p62 ablation or autophagy inhibition with hydroxychloroquine (HCQ) impaired CAF activation and reduced transforming growth factor beta (TGFβ) production, which impeded tumor growth. During CAF activation, p62-induced autophagy up-regulated the expression of the anti-oxidant signaling protein, nuclear factor erythroid 2-related factor 2 (Nrf2), and the ER-stress response regulator, activating transcription factor 6 (ATF6). Genetically or pharmacologically inhibiting the Nrf2-ATF6 pathway totally blocked CAF activation and tumor progression. These results demonstrate that p62 is a key modulator of primary lung adenocarcinoma progression. Thus, targeting the p62-Nrf2 autophagy signaling pathway might be a novel, stroma-focused, cancer prevention and/or treatment strategy.
Heminiphilus faecis gen. nov., sp. nov., a member of the family Muribaculaceae, isolated from mouse faeces and emended description of the genus Muribaculum
No full textThe novel strain AM35T was isolated from the faeces of C57BL/6 mice. These cells are strictly anaerobic, gram negative, oxidase negative, catalase positive, rod-shaped and non-motile. The strain produced creamy yellowish colonies on brain heart infusion (BHI) agar with hemin. Growth was investigated at 30-41 °C in the presence of 0.5-1.5% (w/v) NaCl at pH 6.5-8.5. Taxonomic analysis based on 16S rRNA gene sequencing revealed that strain AM35T is affiliated with the family Muribaculaceae and closely related to the genus Muribaculum. The genomic DNA G + C content of strain AM35T was 47.8 mol%. We detected the whole-cell sugars ribose and galactose; meso-2,6-diaminopimelic acid was absent. The major fatty acids (> 10%) were anteiso-C15:0 and iso-C15:0; the major polar lipid was phosphatidylethanolamine. The major respiratory quinones were MK-10 and MK-11. Based on our phylogenetic, phenotypic and chemotaxonomic analyses, strain AM35T represents a novel genus within the family Muribaculaceae, for which we propose the name Heminiphilus faecis gen. nov., sp. nov. The type strain of Heminiphilus faecis gen. nov., sp. nov. is AM35T (= KCTC 15907 T = DSM 110151 T).
Deubiquitinase OTUD5 is a positive regulator of mTORC1 and mTORC2 signaling pathways
No full textThe mammalian Target of Rapamycin (mTOR) pathway regulates a variety of physiological processes, including cell growth and cancer progression. The regulatory mechanisms of these signals are extremely complex and comprise many feedback loops. Here, we identified the deubiquitinating enzyme ovarian tumor domain-containing protein 5 (OTUD5) as a novel positive regulator of the mTOR complex (mTORC) 1 and 2 signaling pathways. We demonstrated that OTUD5 stabilized β-transducin repeat-containing protein 1 (βTrCP1) proteins via its deubiquitinase (DUB) activity, leading to the degradation of Disheveled, Egl-10, and pleckstrin domain-containing mTOR-interacting protein (DEPTOR), which is an inhibitory protein of mTORC1 and 2. We also showed that mTOR directly phosphorylated OTUD5 and activated its DUB activity. RNA sequencing analysis revealed that OTUD5 regulates the downstream gene expression of mTOR. Additionally, OTUD5 depletion elicited several mTOR-related phenotypes such as decreased cell size and increased autophagy in mammalian cells as well as the suppression of a dRheb-induced curled wing phenotype by RNA interference of Duba, a fly ortholog of OTUD5, in Drosophila melanogaster. Furthermore, OTUD5 knockdown inhibited the proliferation of the cancer cell lines with mutations activating mTOR pathway. Our results suggested a positive feedback loop between OTUD5 and mTOR signaling pathway.
Reduction of squalene epoxidase by cholesterol accumulation accelerates colorectal cancer progression and metastasis
No full textBackground & aims: Squalene epoxidase (SQLE), a rate-limiting enzyme in cholesterol biosynthesis, is suggested as a proto-oncogene. Paradoxically, SQLE is degraded by excess cholesterol, and low SQLE is associated with aggressive colorectal cancer (CRC). Therefore, we studied the functional consequences of SQLE reduction in CRC progression.
Methods: Gene and protein expression data and clinical features of CRCs were obtained from public databases and 293 human tissues, analyzed by immunohistochemistry. In vitro studies showed underlying mechanisms of CRC progression mediated by SQLE reduction. Mice were fed a 2% high-cholesterol or a control diet before and after cecum implantation of SQLE genetic knockdown/control CRC cells. Metastatic dissemination and circulating cancer stem cells were demonstrated by in vivo tracking and flow cytometry analysis, respectively.
Results: In vitro studies showed that SQLE reduction helped cancer cells overcome constraints by inducing the epithelial-mesenchymal transition required to generate cancer stem cells. Surprisingly, SQLE interacted with GSK3β and p53. Active GSK3β contributes to the stability of SQLE, thereby increasing cell cholesterol content, whereas SQLE depletion disrupted the GSK3β/p53 complex, resulting in a metastatic phenotype. This was confirmed in a spontaneous CRC metastasis mice model, where SQLE reduction, by a high-cholesterol regimen or genetic knockdown, strikingly promoted CRC aggressiveness through the production of migratory cancer stem cells.
Conclusions: We showed that SQLE reduction caused by cholesterol accumulation aggravates CRC progression via the activation of the β-catenin oncogenic pathway and deactivation of the p53 tumor suppressor pathway. Our findings provide new insights into the link between cholesterol and CRC, identifying SQLE as a key regulator in CRC aggressiveness and a prognostic biomarker.
Understanding plant social networking system: avoiding deleterious microbiota but calling beneficials
No full textPlant association with microorganisms elicits dramatic effects on the local phytobiome and often causes systemic and transgenerational modulation on plant immunity against insect pests and microbial pathogens. Previously, we introduced the concept of the plant social networking system (pSNS) to highlight the active involvement of plants in the recruitment of potentially beneficial microbiota upon exposure to insects and pathogens. Microbial association stimulates the physiological responses of plants and induces the development of their immune mechanisms while interacting with multiple enemies. Thus, beneficial microbes serve as important mediators of interactions among multiple members of the multitrophic, microscopic and macroscopic communities. In this review, we classify the steps of pSNS such as elicitation, signaling, secreting root exudates, and plant protection; summarize, with evidence, how plants and beneficial microbes communicate with each other; and also discuss how the molecular mechanisms underlying this communication are induced in plants exposed to natural enemies. Collectively, the pSNS modulates robustness of plant physiology and immunity and promotes survival potential by helping plants to overcome the environmental and biological challenges.
Draft genome sequence of Peribacillus sp. AGMB 02131 isolated from feces of a Korean cow
No full textPeribacillus sp. AGMB 02131 was isolated from the feces of a Korean cow. Here, we report the draft genome sequence of the strain AGMB 02131 based on Nova SeqTM 6000 sequencing system (Illumina). The genome comprises 70 contigs with a chromosome length of 4,038,965 bp and 38.5% GC content. The draft genome contains 3,806 protein-coding genes, 51 pseudogenes, 112 RNA genes including 17 ribosomal RNA genes (7 5S rRNA, 7 16S rRNA, 3 23S rRNA), 90 transfer RNA (tRNA) genes, and 5 non-coding RNA (ncRNA) genes. Additionally, genes involved in the fatty acid metabolism (biosynthesis, elongation, and degradation) and bile acid biosynthesis (primary and secondary) were identified throughout the draft genome, which might be crucial for promoting gut epithelial lining to regulate the animal’s health and digestion. Moreover, insulin, antimicrobial, and antineoplastic drug resistance-related genes were also presented in this genome.
Estrogen-related receptor γ increases poly(I:C)-mediated type I IFN expression in mouse macrophages
No full textAlthough type I IFNs (IFN？I) are important for the innate and adaptive immune responses to suppress viral replication, prolonged IFN？I signaling in macrophages suppresses the immune response. Nuclear receptor estrogen？related receptor γ (ERRγ) regulates the transcription of genes involved in endocrine and metabolic functions. However, the role of ERRγ in macrophage immune responses to viruses remains largely unknown. ERRγ expression was significantly induced in mouse bone marrow？derived macrophages (BMDMs) treated with polyinosinic？polycytidylic acid (poly(I:C)). Our results indicated that the induction of ERRγ expression by poly(I:C) is mediated through activation of the cytoplasmic dsRNA receptors, retinoic acid？inducible gene I and melanoma differentiation？associated protein 5. In BMDMs, overexpression of ERRγ significantly increased gene expression and secretion of the IFN？I genes, IFN？α and IFN？β, whereas abolition of ERRγ significantly attenuated poly(I:C)？mediated IFN？I secretion. Chromatin immunoprecipitation assays and mutation analyses of the IFN？I promoters revealed that ERRγ regulates the transcription of IFN？α and IFN？β by binding to a conserved ERR response element in each promoter region. Finally, GSK5182 significantly suppressed poly(I:C)？mediated induction of IFN？I gene expression and secretion in BMDMs. Taken together, these findings reveal a previously unrecognized role for ERRγ in the transcriptional control of innate and adaptive immune response to dsRNA virus replication.