• 제목/요약/키워드: Major regulatory pathways

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Small RNA biology is systems biology

  • Jost, Daniel;Nowojewski, Andrzej;Levine, Erel
    • BMB Reports
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    • 제44권1호
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    • pp.11-21
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    • 2011
  • During the last decade small regulatory RNA (srRNA) emerged as central players in the regulation of gene expression in all kingdoms of life. Multiple pathways for srRNA biogenesis and diverse mechanisms of gene regulation may indicate that srRNA regulation evolved independently multiple times. However, small RNA pathways share numerous properties, including the ability of a single srRNA to regulate multiple targets. Some of the mechanisms of gene regulation by srRNAs have significant effect on the abundance of free srRNAs that are ready to interact with new targets. This results in indirect interactions among seemingly unrelated genes, as well as in a crosstalk between different srRNA pathways. Here we briefly review and compare the major srRNA pathways, and argue that the impact of srRNA is always at the system level. We demonstrate how a simple mathematical model can ease the discussion of governing principles. To demonstrate these points we review a few examples from bacteria and animals.

스트레스와 면역기능 (Stress and Immune Function)

  • 고경봉
    • 정신신체의학
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    • 제4권1호
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    • pp.146-154
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    • 1996
  • 스트레스와 면역기능 간의 관계는 중추신경계, 신경내분비계 및 면역계 간의 의사소통 즉 상호작용에 의해 이루어지고 있다. 중추신경계와 면역계가 상호작용하는 주요 경로는 임파조직의 신경계 wiring system과 신경내분비계다. 면역계는 neuropeptide를 생성하고 이것은 면역반응을 조절한다. 정신사회적 인자와 면역기능 간의 중개자로는 뇌하수체에서 방출되는 peptide, hormone 및 자율신경계 물질이 있다. 시상하부는 내분비계, 신경계 및 면역계를 통합하는 역활을 한다. 특히 시상하부의 paraventricular nucleus가 이 일에 중추적인 역할을 담당한다. 한편 내분비계는 면역계에 의해서 휘이드백을 받는다. 뇌하수체가 면역계를 조절하는 주요 경로로는 시상하부-뇌하수체-부신-흉선축, 시상하부-뇌하수체-성선-흉선축, 송과선-시상하부-뇌하수체축 등이 시사되고 있다. 스트레스와 면역계 간에는 양 방향의 경로가 있는 것으로 가정된다. 즉 스트레스가 면역계에 영향을 미칠 뿐만 아니라 면역계가 정신사회적 기능에 영향을 미칠 수 있다. 따라서 스트레스와 면역기능 간의 관계를 규명하기 위해서는 면역계, 내분비계, 자율신경계 및 뇌활동을 동시에 측정, 비교하여 이들을 통합할 필요가 있다.

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Comparative co-expression analysis of RNA-Seq transcriptome revealing key genes, miRNA and transcription factor in distinct metabolic pathways in diabetic nerve, eye, and kidney disease

  • Asmy, Veerankutty Subaida Shafna;Natarajan, Jeyakumar
    • Genomics & Informatics
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    • 제20권3호
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    • pp.26.1-26.19
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    • 2022
  • Diabetes and its related complications are associated with long term damage and failure of various organ systems. The microvascular complications of diabetes considered in this study are diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. The aim is to identify the weighted co-expressed and differentially expressed genes (DEGs), major pathways, and their miRNA, transcription factors (TFs) and drugs interacting in all the three conditions. The primary goal is to identify vital DEGs in all the three conditions. The overlapped five genes (AKT1, NFKB1, MAPK3, PDPK1, and TNF) from the DEGs and the co-expressed genes were defined as key genes, which differentially expressed in all the three cases. Then the protein-protein interaction network and gene set linkage analysis (GSLA) of key genes was performed. GSLA, gene ontology, and pathway enrichment analysis of the key genes elucidates nine major pathways in diabetes. Subsequently, we constructed the miRNA-gene and transcription factor-gene regulatory network of the five gene of interest in the nine major pathways were studied. hsa-mir-34a-5p, a major miRNA that interacted with all the five genes. RELA, FOXO3, PDX1, and SREBF1 were the TFs interacting with the major five gene of interest. Finally, drug-gene interaction network elucidates five potential drugs to treat the genes of interest. This research reveals biomarker genes, miRNA, TFs, and therapeutic drugs in the key signaling pathways, which may help us, understand the processes of all three secondary microvascular problems and aid in disease detection and management.

Characteristics of 14-3-3 Proteins and Their Role in Plant Immunity

  • Oh, Chang-Sik
    • The Plant Pathology Journal
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    • 제26권1호
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    • pp.1-7
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    • 2010
  • Phosphorylation is a major post-translational modification of proteins that regulate diverse signal transduction pathways in eukaryotic cells. 14-3-3 proteins are regulatory proteins that bind to target proteins in a phosphorylation-dependent manner and have been shown to play an important role in plant growth and development, primary metabolism, and signal transduction. Because phosphorylation plays a critical role in signal transduction pathways to trigger plant immunity, involvement of 14-3-3 proteins in plant immunity has been suggested for a long time. Recent studies have provided new evidence to support a role for 14-3-3 proteins in plant immunity. This review will briefly discuss general characteristics of 14-3-3 proteins and their involvement in plant immunity.

The central regulator p62 between ubiquitin proteasome system and autophagy and its role in the mitophagy and Parkinson's disease

  • Shin, Woo Hyun;Park, Joon Hyung;Chung, Kwang Chul
    • BMB Reports
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    • 제53권1호
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    • pp.56-63
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    • 2020
  • The ubiquitin-proteasome system (UPS) and autophagy are two major degradative pathways of proteins in eukaryotic cells. As about 30% of newly synthesized proteins are known to be misfolded under normal cell conditions, the precise and timely operation of the UPS and autophagy to remove them as well as their tightly controlled regulation, is so important for proper cell function and survival. In the UPS, target proteins are labeled by small proteins called ubiquitin, which are then transported to the proteasome complex for degradation. Alternatively, many greatly damaged proteins are believed to be delivered to the lysosome for autophagic degradation. Although these autophagy and UPS pathways have not been considered to be directly related, many recent studies proposed their close link and dynamic interconversion. In this review, we'll focus on the several regulatory molecules that function in both UPS and autophagy and their crosstalk. Among the proposed multiple modulators, we will take a closer look at the so-called main connector of UPS-autophagy regulation, p62. Last, the functional role of p62 in the mitophagy and its implication for the pathogenesis of Parkinson's disease, one of the major neurodegenerative diseases, will be briefly reviewed.

Regulatory Role of Zinc in Immune Cell Signaling

  • Kim, Bonah;Lee, Won-Woo
    • Molecules and Cells
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    • 제44권5호
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    • pp.335-341
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    • 2021
  • Zinc is an essential micronutrient with crucial roles in multiple facets of biological processes. Dysregulated zinc homeostasis impairs overall immune function and resultantly increases susceptibility to infection. Clinically, zinc supplementation is practiced for treatment of several infectious diseases, such as diarrhea and malaria. Recent focus on zinc as a beneficial element for immune system support has resulted in investigation of the immunomodulatory roles of zinc in a variety of immune cells. Besides its classical role as a cofactor that regulates the structural function of thousands of proteins, accumulating evidence suggests that zinc also acts, in a manner similar to calcium, as an ionic regulator of immune responses via participation as an intracellular messenger in signaling pathways. In this review, we focus on the role of zinc as a signaling molecule in major pathways such as those downstream of Toll-like receptors-, T cell receptor-, and cytokine-mediated signal transduction that regulate the activity and function of monocytes/macrophages and T cells, principal players in the innate and adaptive immune systems.

Application of Pac-Bio Sequencing, Trinity, and rnaSPAdes Assembly for Transcriptome Analysis in Medicinal Crop Astragalus membranaceus

  • Ji-Nam Kang;Si Myung Lee
    • 한국작물학회:학술대회논문집
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    • 한국작물학회 2022년도 추계학술대회
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    • pp.254-254
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    • 2022
  • Astragalus membranaceus (A. membranaceus) has traditionally been used as a medicinal plant in East Asia for the treatment ofvarious diseases. A. membranaceus belongs to the legume family and is known to be rich in substances such as flavonoids and saponins. Recent pharmacological studies of A. membranaceus have shown that the plant has immunomodulatory, anti-oxidant, anti-cancer, and anti-inflammatory effects. However, knowledge of major biosynthetic pathways in A. membranaceu is still lacking. Recently developed sequencing techniques enable high-quality transcriptome analysis in plants, which is recognized as an important part in elucidating the regulatory mechanisms of many plant secondary metabolic pathways. However, it is difficult to predict the number of transcripts because plant transcripts contain a large number of isoforms due to alternative splicing events, which can vary depending on the assembly platform used. In this study, we constructed three unigene sets using Pac-Bio isoform sequencing, Trinity and rnaSPAdes assembly for detailed transcriptome analysis mA. membranaceus. Furthermore, all genes involved in the flavonoid biosynthetic pathway were searched from three unigene sets, and structural comparisons and expression profiles between these genes were analyzed. The isoflavone synthesis was active in most tissues. Flavonol synthesis was mainly active in leaves and flowers, and anthocyanin synthesis was specific in flowers. Gene structural analysis revealed structural differences in the flavonoid-related genes derived from the three unigene sets. This study suggests the need for the application of multiple unigene sets for the analysis of key biosynthetic pathways in plants.

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Michael addition acceptor 그룹을 가지고 있는 phytochemicals의 toll-like receptor 신호전달체계 조절을 통한 항염증 효과 (Anti-inflammatory Effects of Phytochemicals Having Michael Addition Acceptors by the Modulation of Toll-like Receptor Signaling Pathways)

  • 윤형선
    • 한국식품과학회지
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    • 제41권5호
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    • pp.477-482
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    • 2009
  • TLRs는 여러 병원균들이 가지고 있는 PAMPs를 인식해서, 선천성 면역 반응을 유도하는 중요한 역할을 한다. TLR4의 이합체 형성은 신호전달 체계의 활성화와 뒤이어 발생하는 선천성 면역 반응을 유도하기 위해서 최초로 일어나는 반응으로 알려져 있다. 우리가 먹는 식품 중에는 항염증 효과가 있다고 널리 알려져 있는 phytochemicals이 포함되어 있다. 특히 ${\alpha},{\beta}$-unsaturated carbonyl group을 가지고 있는 curcumin, 6-shogaol, 그리고 cinnamaldehyde는 Michael addition 반응에 의해서 LPS에 의해서 유도된 TLR4의 이합체 형성을 억제시켜, 전사요소 NF-${\kappa}B$와 IRF3 활성화 및 그것들에 의해서 조절되는 타깃 유전자들을 억제시킨다. 이러한 결과는 ${\alpha},{\beta}$-unsaturated carbonyl group을 가지고 있는 curcumin, 6-shogaol, 그리고 cinnamaldehyde의 항염증 효능에 대한 새로운 기전을 설명해 주는 것이라 할 수 있겠다.

Potential benefits of ginseng against COVID-19 by targeting inflammasomes

  • Yi, Young-Su
    • Journal of Ginseng Research
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    • 제46권6호
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    • pp.722-730
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    • 2022
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogenic virus that causes coronavirus disease 2019 (COVID-19), with major symptoms including hyper-inflammation and cytokine storm, which consequently impairs the respiratory system and multiple organs, or even cause death. SARS-CoV-2 activates inflammasomes and inflammasome-mediated inflammatory signaling pathways, which are key determinants of hyperinflammation and cytokine storm in COVID-19 patients. Additionally, SARS-CoV-2 inhibits inflammasome activation to evade the host's antiviral immunity. Therefore, regulating inflammasome initiation has received increasing attention as a preventive measure in COVID-19 patients. Ginseng and its major active constituents, ginsenosides and saponins, improve the immune system and exert anti-inflammatory effects by targeting inflammasome stimulation. Therefore, this review discussed the potential preventive and therapeutic roles of ginseng in COVID-19 based on its regulatory role in inflammasome initiation and the host's antiviral immunity.

Novel target genes of hepatocellular carcinoma identified by chip-based functional genomic approaches

  • Kim Dong-Min;Min Sang-Hyun;Lee Dong-Chul;Park Mee-Hee;Lim Soo-Jin;Kim Mi-Na;Han Sang-Mi;Jang Ye-Jin;Yang Suk-Jin;Jung Hai-Yong;Byun Sang-Soon;Lee Jeong-Ju;Oh Jung-Hwa
    • 한국생물정보학회:학술대회논문집
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    • 한국생물정보시스템생물학회 2006년도 Principles and Practice of Microarray for Biomedical Researchers
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    • pp.83-89
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    • 2006
  • Cellular functions are carried out by a concerted action of biochemical pathways whose components have genetic interactions. Abnormalities in the activity of the genes that constitute or modulate these pathways frequently have oncogenic implications. Therefore, identifying the upstream regulatory genes for major biochemical pathways and defining their roles in carcinogenesis can have important consequences in establishing an effective target-oriented antitumor strategy We have analyzed the gene expression profiles of human liver cancer samples using cDNA microarray chips enriched in liver and/or stomach-expressed cDNA elements, and identified groups of genes that can tell tumors from non-tumors or normal liver, or classify tumors according to clinical parameters such as tumor grade, age, and inflammation grade. We also set up a high-throughput cell-based assay system (cell chip) that can monitor the activity of major biochemical pathways through a reporter assay. Then, we applied the cell chip platform for the analysis of the HCC-associated genes discovered from transcriptome profiling, and found a number of cancer marker genes having a potential of modulating the activity of cancer-related biochemical pathways such as E2F, TCF, p53, Stat, Smad, AP-1, c-Myc, HIF and NF-kB. Some of these marker genes were previously blown to modulate these pathways, while most of the others not. Upon a fast-track phenotype analysis, a subset of the genes showed increased colony forming abilities in soft agar and altered cell morphology or adherence characteristics in the presence of purified matrix proteins. We are currently analyzing these selected marker genes in more detail for their effects on various biological Processes and for Possible clinical roles in liver cancer development.

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