• Title/Summary/Keyword: response regulators

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Complement regulation: physiology and disease relevance

  • Cho, Heeyeon
    • Clinical and Experimental Pediatrics
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    • v.58 no.7
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    • pp.239-244
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    • 2015
  • The complement system is part of the innate immune response and as such defends against invading pathogens, removes immune complexes and damaged self-cells, aids organ regeneration, confers neuroprotection, and engages with the adaptive immune response via T and B cells. Complement activation can either benefit or harm the host organism; thus, the complement system must maintain a balance between activation on foreign or modified self surfaces and inhibition on intact host cells. Complement regulators are essential for maintaining this balance and are classified as soluble regulators, such as factor H, and membrane-bound regulators. Defective complement regulators can damage the host cell and result in the accumulation of immunological debris. Moreover, defective regulators are associated with several autoimmune diseases such as atypical hemolytic uremic syndrome, dense deposit disease, age-related macular degeneration, and systemic lupus erythematosus. Therefore, understanding the molecular mechanisms by which the complement system is regulated is important for the development of novel therapies for complement-associated diseases.

Positive and negative regulation of the Drosophila immune response

  • Aggarwal, Kamna;Silverman, Neal
    • BMB Reports
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    • v.41 no.4
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    • pp.267-277
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    • 2008
  • Insects mount a robust innate immune response against a wide array of microbial pathogens. The hallmark of the Drosophila humoral immune response is the rapid production of anti-microbial peptides in the fat body and their release into the circulation. Two recognition and signaling cascades regulate expression of these antimicrobial peptide genes. The Toll pathway is activated by fungal and many Gram-positive bacterial infections, whereas the immune deficiency (IMD) pathway responds to Gram-negative bacteria. Recent work has shown that the intensity and duration of the Drosophila immune response is tightly regulated. As in mammals, hyperactivated immune responses are detrimental, and the proper down-modulation of immunity is critical for protective immunity and health. In order to keep the immune response properly modulated, the Toll and IMD pathways are controlled at multiple levels by a series of negative regulators. In this review, we focus on recent advances identifying and characterizing the negative regulators of these pathways.

Cell Cycle and Cancer

  • Park, Moon-Taek;Lee, Su-Jae
    • BMB Reports
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    • v.36 no.1
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    • pp.60-65
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    • 2003
  • Cancer is frequently considered to be a disease of the cell cycle. As such, it is not surprising that the deregulation of the cell cycle is one of the most frequent alterations during tumor development. Cell cycle progression is a highly-ordered and tightly-regulated process that involves multiple checkpoints that assess extracellular growth signals, cell size, and DNA integrity. Cyclin-dependent kinases (CDKs) and their cyclin partners are positive regulators of accelerators that induce cell cycle progression; whereas, cyclin-dependent kinase inhibitors (CKIs) that act as brakes to stop cell cycle progression in response to regulatory signals are important negative regulators. Cancer originates from the abnormal expression of activation of positive regulators and functional suppression of negative regulators. Therefore, understanding the molecular mechanisms of the deregulation of cell cycle progression in cancer can provide important insights into how normal cells become tumorigenic, as well as how cancer treatment strategies can be designed.

Influence of plant growth regulators on adventitious shoot formation of Glehnia littoralis Fr. Schmid (갯방풍의 기내부정아 형성에 미치는 식물생정조절물질의 영향)

  • Choo, Byung-Kil;Ji, Yun-Ui;Moon, Byeong-Cheol;Choi, Go-Ya;Lee, Hye-Won;Lee, A-Yeong;Kim, Ho-Kyoung
    • Korean Journal of Oriental Medicine
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    • v.14 no.1
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    • pp.113-116
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    • 2008
  • Petiole explant of Glehnia littoralis Fr. Schmidt was in vitro cultured MS plant medium(DUCHEFA co.) supplemented with various plant growth regulators and examined to find out their optimum combination and concentration for plantlet regeneration. We investigated optimal condition for efficient plant regeneration through adventitious shoot formation on MS plant medium with various kinds of plant growth regulators. Embryogenic calli and adventitious shoot formation were greatly influenced by plant growth regulators. Embryogenic calli induction showed a good response on MS medium supplemented with NAA and BA than others. Especially, combination of 1.0 mg/L NAA and 0.5 mg/L BA on MS medium led to the greatest frequency in adventitious shoot. The results suggest that plant regulator selection be important factor to achieve an efficient regeneration.

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Role of RUNX Family Transcription Factors in DNA Damage Response

  • Samarakkody, Ann Sanoji;Shin, Nah-Young;Cantor, Alan B.
    • Molecules and Cells
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    • v.43 no.2
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    • pp.99-106
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    • 2020
  • Cells are constantly exposed to endogenous and exogenous stresses that can result in DNA damage. In response, they have evolved complex pathways to maintain genomic integrity. RUNX family transcription factors (RUNX1, RUNX2, and RUNX3 in mammals) are master regulators of development and differentiation, and are frequently dysregulated in cancer. A growing body of research also implicates RUNX proteins as regulators of the DNA damage response, often acting in conjunction with the p53 and Fanconi anemia pathways. In this review, we discuss the functional role and mechanisms involved in RUNX factor mediated response to DNA damage and other cellular stresses. We highlight the impact of these new findings on our understanding of cancer predisposition associated with RUNX factor dysregulation and their implications for designing novel approaches to prevent cancer formation in affected individuals.

Sirtuins in Cancer: a Balancing Act between Genome Stability and Metabolism

  • Jeong, Seung Min;Haigis, Marcia C.
    • Molecules and Cells
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    • v.38 no.9
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    • pp.750-758
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    • 2015
  • Genomic instability and altered metabolism are key features of most cancers. Recent studies suggest that metabolic reprogramming is part of a systematic response to cellular DNA damage. Thus, defining the molecules that fine-tune metabolism in response to DNA damage will enhance our understanding of molecular mechanisms of tumorigenesis and have profound implications for the development of strategies for cancer therapy. Sirtuins have been established as critical regulators in cellular homeostasis and physiology. Here, we review the emerging data revealing a pivotal function of sirtuins in genome maintenance and cell metabolism, and highlight current advances about the phenotypic consequences of defects in these critical regulators in tumorigenesis. While many questions should be addressed about the regulation and context-dependent functions of sirtuins, it appears clear that sirtuins may provide a promising, exciting new avenue for cancer therapy.

Inhibition of the DevSR Two-Component System by Overexpression of Mycobacterium tuberculosis PknB in Mycobacterium smegmatis

  • Bae, Hyun-Jung;Lee, Ha-Na;Baek, Mi-Na;Park, Eun-Jin;Eom, Chi-Yong;Ko, In-Jeong;Kang, Ho-Young;Oh, Jeong-Il
    • Molecules and Cells
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    • v.40 no.9
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    • pp.632-642
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    • 2017
  • The DevSR (DosSR) two-component system, which is a major regulatory system involved in oxygen sensing in mycobacteria, plays an important role in hypoxic induction of many genes in mycobacteria. We demonstrated that overexpression of the kinase domain of Mycobacterium tuberculosis (Mtb) PknB inhibited transcriptional activity of the DevR response regulator in Mycobacterium smegmatis and that this inhibitory effect was exerted through phosphorylation of DevR on Thr180 within its DNA-binding domain. Moreover, the purified kinase domain of Mtb PknB significantly phosphorylated RegX3, NarL, KdpE, TrcR, DosR, and MtrA response regulators of Mtb that contain the Thr residues corresponding to Thr180 of DevR in their DNA-binding domains, implying that transcriptional activities of these response regulators might also be inhibited when the kinase domain of PknB is overexpressed.

Role of Regulators of G-Protein Signaling 4 in $Ca^{2+}$ Signaling in Mouse Pancreatic Acinar Cells

  • Park, Soon-Hong;Lee, Syng-Ill;Shin, Dong-Min
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.6
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    • pp.383-388
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    • 2011
  • Regulators of G-protein signaling (RGS) proteins are regulators of $Ca^{2+}$ signaling that accelerate the GTPase activity of the G-protein ${\alpha}$ -subunit. RGS1, RGS2, RGS4, and RGS16 are expressed in the pancreas, and RGS2 regulates G-protein coupled receptor (GPCR)-induced $Ca^{2+}$ oscillations. However, the role of RGS4 in $Ca^{2+}$ signaling in pancreatic acinar cells is unknown. In this study, we investigated the mechanism of GPCR-induced $Ca^{2+}$ signaling in pancreatic acinar cells derived from $RGS4^{-/-}$ mice. $RGS4^{-/-}$ acinar cells showed an enhanced stimulus intensity response to a muscarinic receptor agonist in pancreatic acinar cells. Moreover, deletion of RGS4 increased the frequency of $Ca^{2+}$ oscillations. $RGS4^{-/-}$ cells also showed increased expression of sarco/endoplasmic reticulum $Ca^{2+}$ ATPase type 2. However, there were no significant alterations, such as $Ca^{2+}$ signaling in treated high dose of agonist and its related amylase secretion activity, in acinar cells from $RGS4^{-/-}$ mice. These results indicate that RGS4 protein regulates $Ca^{2+}$ signaling in mouse pancreatic acinar cells.

Genetic Responses to Metal ion in Aslmonella typhimurium (Salmonella typhimurium의 금속이온에 대한 유전적 반응)

  • Jung, Ju-Ri;Park, Kyeong-Ryang;Koh, Sang-Kyun;Park, Yong-Keun;Lee, In-Soo
    • Journal of Life Science
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    • v.8 no.2
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    • pp.216-225
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    • 1998
  • Metal ion-induced and it’s regulatory genes were screened in virulent salmonella typhimurium UK1 and tested cross-regulation with various stresses. Using the techniqud of P22-MudJ(Km, lacZ)-directed lacZ operon fusion, LF40 cuiA::MudJ and Lf153 cuiD::MudJ which were induced by copper were selected. cuia and cuiD were determined anaerobic coper inducible and copper tolerance response gene, respectively. Also cuiA and cuiD locus were determined at 81 and 8min, respectively, on salmonella Genetic Map. The two regulators were identified as cuaR, and cudR, which controls cuiA and cuiD, respectively. cuaR, and cudR appeared as negative regulators because the expression of cuiA-lac-Z and cuiD-lacZ were increased. Copper adapted UK1 showed high resistance to H$_{2}$O$_{2}$, but cuiD did not. The product of the cudR locus was responsible for decreasing the tolerance to copper and H$_{2}$O$_{2}$. Furthemore cuiA and cuiD locus were found to be part of a regulon under the control of a trans-acting regulators, rpoS, oxyR and relA. Therefore, the results suggest CTR participate with oxidative stress on Salmonella.

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A Study on Performance Characteristics for a CNG Regulators of Automotive Vehicle (차량용 CNG 레귤레이터의 성능특성에 관한 연구)

  • Kim, Chang-Gi;Park, Cheol-Woong
    • Journal of the Korean Institute of Gas
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    • v.11 no.4
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    • pp.12-16
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    • 2007
  • The fuel pressure regulator mounted on CNG vehicles is used to maintain a constant pressure in the fuel injection system. It needs precise fuel pressure control to obtain benefits of high efficiency and low emissions in CNG vehicles. In this study, a high pressure test rig for the performance evaluation of CNG regulators was introduced. Two different CNG regulators were tested and compared each other at various test conditions. Results showed that dynamic response and creep characteristics are directly effected by the valve assembly design. Gas temperature was dramatically dropped at hish supply pressure conditions, so that effective design for coolant bowl is needed to prevent icing problem.

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