• Title/Summary/Keyword: Regulatory mechanisms

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The Role of Cell Cycle Regulators in Normal and Malignant Cell Proliferation

  • Lee, Jin-Hwa
    • Biomedical Science Letters
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    • v.16 no.2
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    • pp.71-74
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    • 2010
  • Cell proliferation is governed by precise and orderly process the regulation of which involves many different proteins. The key enzyme for cell growth and arrest is cyclin dependent kinases (cdks). In human cells, several cdks orchestrate four distinct cell cycle phases (M, $G_1$, S and $G_2$ ) and they sequentially operate in an order of cdc1, cdk4, cdk6 and cdk2. The regulatory components of cdks consist of cyclins and two family of cdk inhibitors, INK4 (inhibitors of cdk4) and KIP (kinase inhibitor protein). $G_1$ regulatory molecules for cdk mainly respond to environmental cues of mitogenic and anti-mitogenic stimuli and therefore influence activities of $G_1$ cdks, namely, cdk4/6 and cdk2. $G_1$ inhibitors include $p21^{CIP}$ and $p27^{KIP1}$. Between them, $p27^{KIP1}$ has attracted attentions of many researchers because of its characteristic regulatory features and diverse functions. Besides, the role of $p27^{KIP1}$ in cancer development warrants further studies in the future. Therefore, this review will focus on the recent findings and especially on the complexity of regulatory mechanisms of $p27^{KIP1}$.

Transcriptome Analysis of Phosphate Starvation Response in Escherichia coli

  • Baek, Jong-Hwan;Lee, Sang-Yup
    • Journal of Microbiology and Biotechnology
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    • v.17 no.2
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    • pp.244-252
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    • 2007
  • Escherichia coli has a PhoR-PhoB two-component regulatory system to detect and respond to the changes of environmental phosphate concentration. For the E. coli W3110 strain growing under phosphate-limiting condition, the changes of global gene expression levels were investigated by using DNA microarray analysis. The expression levels of some genes that are involved in phosphate metabolism were increased as phosphate became limited, whereas those of the genes involved in ribosomal protein or amino acid metabolism were decreased, owing to the stationary phase response. The upregulated genes could be divided into temporarily and permanently inducible genes by phosphate starvation. At the peak point showing the highest expression levels of the phoB and phoR genes under phosphate-limiting condition, the phoB- and/or phoR-dependent regulatory mechanisms were investigated in detail by comparing the gene expression levels among the wild-type and phoB and/or phoR mutant strains. Overall, the phoB mutation was epistatic over the phoR mutation. It was found that PhoBR and PhoB were responsible for the upregulation of the phosphonate or glycerol phosphate metabolism and high-affinity phosphate transport system, respectively. These results show the complex regulation by the PhoR-PhoB two-component regulatory system in E. coli.

Regulatory Mechanism of Spindle Movements during Oocyte Meiotic Division

  • Ai, Jun-Shu;Li, Mo;Schatten, Heide;Sun, Qing-Yuan
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.11
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    • pp.1477-1486
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    • 2009
  • Female germ cell meiotic divisions are typically asymmetric, giving rise to two daughter cells with different sizes. Spindle movements including spindle migration from the oocyte center to the cortex and spindle rotation from parallel to perpendicular (typically in the mouse) at the cortex are crucial for these asymmetric divisions and therefore are crucial for gamete production. Different regulatory mechanisms for spindle movements have been determined in different species and a wide variety of different molecular components and processes that are involved in spindle movements have also been identified in different species. Here, we review the current state of knowledge as well as our understanding of mechanisms for spindle movements in different systems with focus on three main aspects: microtubules (MT), microfilaments (MF) and molecules associated with cytoskeletal organization as well as molecules that are not directly related to the cytoskeleton. How they might interact or function independently during female meiotic divisions in different species is discussed in detail.

Recent research progress on the functional roles and regulatory mechanisms of SMALL AUXIN UP RNA gene family (SMALL AUXIN UP RNA 유전자 집단의 기능과 조절 메커니즘에 대한 최근 연구 동향)

  • Lee, Sang Ho
    • Journal of Plant Biotechnology
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    • v.45 no.3
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    • pp.183-189
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    • 2018
  • The plant hormone auxin regulates the overall metabolic processes essential for plant growth and development. Auxin signaling is mediated by early auxin response genes, which are classified into three major families: AUXIN/INDOLE ACETIC ACID (AUX/IAA), GRETCHEN HAGEN3 (GH3) and SMALL AUIN UP RNA (SAUR). The SAUR gene family is the largest family among early auxin response genes and encodes the small and highly unstable gene products. The functional roles of SAUR genes have remained unclear for many years. The traditional genetic and molecular studies on the SAUR functions have been hampered by their likely genetic redundancy and tandem arrays of highly related genes in the plant genome, together with the molecular characteristics of SAUR. However, recent studies have suggested possible roles of SAUR in a variety of tissues and developmental stages in accordance with the novel approaches such as gain-of-function and RNA silencing techniques. In this review, the recent research progress on the functional roles and regulatory mechanisms of SAUR and a set of possible future works are discussed.

Epidermal Growth Factor Receptor-Related DNA Repair and Radiation-Resistance Regulatory Mechanisms: A Mini-Review

  • Bai, Jing;Guo, Xiao-Guang;Bai, Xiao-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.4879-4881
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    • 2012
  • Epidermal growth factor receptor (EGFR) overexpression is associated with resistance to chemotherapy and radiotherapy. The EGFR modulates DNA repair after radiation-induced damage through an association with the catalytic subunit of DNA protein kinase. DNA double-strand breaks (DSBs) are the most lethal type of DNA damage induced by ionizing radiation, and non-homologous end joining is the predominant pathway for repair of radiation-induced DSBs. Some cell signaling pathways that respond to normal growth factors are abnormally activated in human cancer. These pathways also invoke the cell survival mechanisms that lead to resistance to radiation. The molecular connection between the EGFR and its control over DNA repair capacity appears to be mediated by one or more signaling pathways downstream of this receptor. The purpose of this mini-review was not only to highlight the relation of the EGFR signal as a regulatory mechanism to DNA repair and radiation resistance, but also to provide clues to improving existing radiation resistance through novel therapies based on the above-mentioned mechanism.

The Role of Dendritic Cells in Central Tolerance

  • Oh, Jaehak;Shin, Jeoung-Sook
    • IMMUNE NETWORK
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    • v.15 no.3
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    • pp.111-120
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    • 2015
  • Dendritic cells (DCs) play a significant role in establishing self-tolerance through their ability to present self-antigens to developing T cells in the thymus. DCs are predominantly localized in the medullary region of thymus and present a broad range of self-antigens, which include tissue-restricted antigens expressed and transferred from medullary thymic epithelial cells, circulating antigens directly captured by thymic DCs through coticomedullary junction blood vessels, and peripheral tissue antigens captured and transported by peripheral tissue DCs homing to the thymus. When antigen-presenting DCs make a high affinity interaction with antigen-specific thymocytes, this interaction drives the interacting thymocytes to death, a process often referred to as negative selection, which fundamentally blocks the self-reactive thymocytes from differentiating into mature T cells. Alternatively, the interacting thymocytes differentiate into the regulatory T (Treg) cells, a distinct T cell subset with potent immune suppressive activities. The specific mechanisms by which thymic DCs differentiate Treg cells have been proposed by several laboratories. Here, we review the literatures that elucidate the contribution of thymic DCs to negative selection and Treg cell differentiation, and discusses its potential mechanisms and future directions.

Small RNA biology is systems biology

  • Jost, Daniel;Nowojewski, Andrzej;Levine, Erel
    • BMB Reports
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    • v.44 no.1
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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.

Proteomic Comparison of Gibberella moniliformis in Limited-Nitrogen (Fumonisin-Inducing) and Excess-Nitrogen (Fumonisin-Repressing) Conditions

  • Choi, Yoon-E;Butchko, Robert A.E.;Shim, Won-Bo
    • Journal of Microbiology and Biotechnology
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    • v.22 no.6
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    • pp.780-787
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    • 2012
  • The maize pathogen Gibberella moniliformis produces fumonisins, a group of mycotoxins associated with several disorders in animals and humans, including cancer. The current focus of our research is to understand the regulatory mechanisms involved in fumonisin biosynthesis. In this study, we employed a proteomics approach to identify novel genes involved in the fumonisin biosynthesis under nitrogen stress. The combination of genome sequence, mutant strains, EST database, microarrays, and proteomics offers an opportunity to advance our understanding of this process. We investigated the response of the G. moniliformis proteome in limited nitrogen (N0, fumonisin-inducing) and excess nitrogen (N+, fumonisin-repressing) conditions by one- and two-dimensional electrophoresis. We selected 11 differentially expressed proteins, six from limited nitrogen conditions and five from excess nitrogen conditions, and determined the sequences by peptide mass fingerprinting and MS/MS spectrophotometry. Subsequently, we identified the EST sequences corresponding to the proteins and studied their expression profiles in different culture conditions. Through the comparative analysis of gene and protein expression data, we identified three candidate genes for functional analysis and our results provided valuable clues regarding the regulatory mechanisms of fumonisin biosynthesis.

Functions of Metallothionein Generating Interleukin-10-Producing Regulatory $CD4^{+}T$ Cells Potentiate Suppression of Collagen-Induced Arthritis

  • Huh, Sung-Jin;Lee, Kyu-Heon;Yun, Hye-Sun;Paik, Doo-Jin;Kim, Jung-Mogg;Youn, Jee-Hee
    • Journal of Microbiology and Biotechnology
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    • v.17 no.2
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    • pp.348-358
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    • 2007
  • Metallothionein, a cysteine-rich stress response protein that is naturally induced by a variety of immunologic stressors, has been shown to suppress autoimmune disorders through mechanisms not yet fully defined. In the present study, we examined the underlying mechanisms by which metallothionein might mediate such regulation of autoimmunity. $Na\ddot{i}ve\;CD4^+$ T cells from metallothionein-deficient mice differentiated to produce significantly less IL-10, $TGF-{\gamma}$, and repressor of GATA, but more $IFN-{\gamma}$ and T-bet, when compared with those from wild-type mice. The levels of IL-4 and GATA-3 production were not different between the two groups of mice. Conversely, treatment with exogenous metallothionein during the priming phase drove $na\ddot{i}ve$ wild-type $CD4^+\;T$ cells to differentiate into cells producing more IL-10 and $TGF-{\beta}$, but less $IFN-{\gamma}$ than untreated cells. Metallothionein-primed cells were hyporesponsive to restimulation, and suppressive to T cell proliferation in an IL-10-dependent manner. Lymphocytes from metallothionein-deficient mice displayed significantly elevated levels of AP-1 and JNK activities in response to stimulation compared with those from wild-type controls. Importantly, transgenic mice overexpressing metallothionein exhibited significantly reduced susceptibility to collagen-induced arthritis and enhanced IL-10 level in the serum, relative to their nontransgenic littermates. Taken together, these data suggest that metallothionein is able to promote the generation of IL-10-and $TGF-{\beta}$-producing type 1 regulatory T-like cells by downregulating JNK-dependent AP-1 activity. Thus, metallothionein may play an important role in the regulation of Th1-dependent autoimmune arthritis, and may represent both a potential target for therapeutic manipulation and a critical element in the diagnostic assessment of disease potential.

Development of the Regulatory Impact Analysis Framework for the Convergence Industry: Case Study on Regulatory Issues by Emerging Industry (융합산업 규제영향분석 프레임워크 개발: 신산업 분야별 규제이슈 사례 연구)

  • Song, Hye-Lim;Seo, Bong-Goon;Cho, Sung-Min
    • Journal of Intelligence and Information Systems
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    • v.27 no.3
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    • pp.199-230
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    • 2021
  • Innovative new products and services are being launched through the convergence between heterogeneous industries, and social interest and investment in convergence industries such as AI, big data-based future cars, and robots are continuously increasing. However, in the process of commercialization of convergence new products and services, there are many cases where they do not conform to the existing regulatory and legal system, which causes many difficulties in companies launching their products and services into the market. In response to these industrial changes, the current government is promoting the improvement of existing regulatory mechanisms applied to the relevant industry along with the expansion of investment in new industries. This study, in these convergence industry trends, aimed to analysis the existing regulatory system that is an obstacle to market entry of innovative new products and services in order to preemptively predict regulatory issues that will arise in emerging industries. In addition, it was intended to establish a regulatory impact analysis system to evaluate adequacy and prepare improvement measures. The flow of this study is divided into three parts. In the first part, previous studies on regulatory impact analysis and evaluation systems are investigated. This was used as basic data for the development direction of the regulatory impact framework, indicators and items. In the second regulatory impact analysis framework development part, indicators and items are developed based on the previously investigated data, and these are applied to each stage of the framework. In the last part, a case study was presented to solve the regulatory issues faced by actual companies by applying the developed regulatory impact analysis framework. The case study included the autonomous/electric vehicle industry and the Internet of Things (IoT) industry, because it is one of the emerging industries that the Korean government is most interested in recently, and is judged to be most relevant to the realization of an intelligent information society. Specifically, the regulatory impact analysis framework proposed in this study consists of a total of five steps. The first step is to identify the industrial size of the target products and services, related policies, and regulatory issues. In the second stage, regulatory issues are discovered through review of regulatory improvement items for each stage of commercialization (planning, production, commercialization). In the next step, factors related to regulatory compliance costs are derived and costs incurred for existing regulatory compliance are calculated. In the fourth stage, an alternative is prepared by gathering opinions of the relevant industry and experts in the field, and the necessity, validity, and adequacy of the alternative are reviewed. Finally, in the final stage, the adopted alternatives are formulated so that they can be applied to the legislation, and the alternatives are reviewed by legal experts. The implications of this study are summarized as follows. From a theoretical point of view, it is meaningful in that it clearly presents a series of procedures for regulatory impact analysis as a framework. Although previous studies mainly discussed the importance and necessity of regulatory impact analysis, this study presented a systematic framework in consideration of the various factors required for regulatory impact analysis suggested by prior studies. From a practical point of view, this study has significance in that it was applied to actual regulatory issues based on the regulatory impact analysis framework proposed above. The results of this study show that proposals related to regulatory issues were submitted to government departments and finally the current law was revised, suggesting that the framework proposed in this study can be an effective way to resolve regulatory issues. It is expected that the regulatory impact analysis framework proposed in this study will be a meaningful guideline for technology policy researchers and policy makers in the future.