• Title/Summary/Keyword: Jab1

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Structural characterization of As-MIF and hJAB1 during the inhibition of cell-cycle regulation

  • Park, Young-Hoon;Jeong, Suk;Ha, Ki-Tae;Yu, Hak Sun;Jang, Se Bok
    • BMB Reports
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    • v.50 no.5
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    • pp.269-274
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    • 2017
  • The biological activities of macrophage migration inhibitory factor (MIF) might be mediated through a classical receptor-mediated or non-classical endocytic pathway. JAB1 (C-Jun activation domain-binding protein-1) promotes the degradation of the tumor suppressor, p53, and the cyclin-dependent kinase inhibitor, p27. When MIF and JAB1 are bound to each other in various intracellular sites, MIF inhibits the positive regulatory effects of JAB1 on the activity of AP-1. The intestinal parasite, Anisakis simplex, has an immunomodulatory effect. The molecular mechanism of action of As-MIF and human JAB1 are poorly understood. In this study, As-MIF and hJAB1 were expressed and purified with high solubility. The structure of As-MIF and hJAB1 interaction was modeled by homology modeling based on the structure of Ace-MIF. This study provides evidence indicating that the MIF domain of As-MIF interacts directly with the MPN domain of hJAB1, and four structure-based mutants of As-MIF and hJAB1 disrupt the As-MIF-hJAB1 interaction.

Jab1 has negative effects on p53-mediated genotoxic stresses

  • Lee, Eun-Woo;Lee, Sang-Sik;Song, Jae-Whan
    • BMB Reports
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    • v.42 no.5
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    • pp.299-303
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    • 2009
  • In this study, we use promoter analysis to show that interaction between Jab1 and p53 induces suppression of p53 activation in U2OS and H1299 cells. Interaction between p53 and Jab1 was further confirmed by immunoprecipitation and immunofluorescent analyses. In particular, Jab1 was able to induce nuclear export of p53 as previously reported. When Jab1 was overexpressed in U2OS cells followed by etoposide or hydrogen peroxide ($H_2O_2$), cell death induced by such stresses was protected against. On the contrary, when the level of Jab1 was suppressed in U2OS cells, cytotoxicity imposed by etoposide and $H_2O_2$ was dramatically increased, suggesting a cell protective role for Jab1. These results indicate that Jab1 is a negative regulator of p53 and a plausible oncogene.

Phosphorylation of p53 at threonine 155 is required for Jab1-mediated nuclear export of p53

  • Lee, Eun-Woo;Oh, Wonkyung;Song, Hosung Paul;Kim, Won Kon
    • BMB Reports
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    • v.50 no.7
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    • pp.373-378
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    • 2017
  • The Jun activation-domain binding protein 1 (Jab1) induces p53 nuclear export and cytoplasmic degradation, but the underlying mechanism is poorly understood. Here, we show that phosphorylation at the threonine 155 residue is essential for Jab1-mediated p53 nuclear export. Jab1 stimulated phosphorylation of p53 at T155 was inhibited by curcumin, an inhibitor of COP9 signalosome (CSN)-associated kinases. The T155E mutant, which mimics phosphorylated p53, exhibited spontaneous cytoplasmic localization in the absence of Jab1. This process was prevented by leptinomycin B (LMB), but not by curcumin. The substitution of threonine 155 for valine (T155V) abrogated Jab1-mediated p53 nuclear export, indicating that phosphorylation at this site is essential for Jab1-mediated regulation of p53. Although T155E can be localized in the cytoplasm in the absence of Mdm2, the translocation of T155E was significantly enhanced by ectopic Hdm2 expression. Our data suggests that Jab1-mediated phosphorylation of p53 at Thr155 residue mediates nuclear export of p53.

Jab1 as a Mediator of Nuclear Export and Cytoplasmic Degradation of p53

  • Lee, Eun-Woo;Oh, Wonkyung;Song, Jaewhan
    • Molecules and Cells
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    • v.22 no.2
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    • pp.133-140
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    • 2006
  • Jun activation domain-binding protein 1 (Jab1) is involved in various cellular mechanisms including development in Drosophila and mouse, cell cycle control and signal transduction pathways. Recent studies also determined that Jab1 functions as a nuclear exporter and inducer of cytoplasmic degradation for several proteins including p53, p27, capsid of West Nile virus, and Smad4/7 proteins. In particular, p53 is shown to bind to and to be exported into the cytoplasm by Jab1, which helps to maintain low levels of p53 under normal conditions. This review was undertaken in an effort to understand the biological significance of the homeostasis of p53 as maintained in the presence of Jab1. Based on our observations, we have provided potential mechanistic hypotheses for the nuclear export of p53 in coordination with Jab1 and the role of other factors in these processes.

Hypoxia-Inducible Factor 1 Promoter-Induced JAB1 Overexpression Enhances Chemotherapeutic Sensitivity of Lung Cancer Cell Line A549 in an Anoxic Environment

  • Hu, Ming-Dong;Xu, Jian-Cheng;Fan, Ye;Xie, Qi-Chao;Li, Qi;Zhou, Chang-Xi;Mao, Mei;Yang, Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2115-2120
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    • 2012
  • The presence of lung cancer cells in anoxic zones is a key cause od chemotherapeutic resistance. Thus, it is necessary to enhance the sensitivity of such lung cancer cells. However, loss of efficient gene therapeutic targeting and inefficient objective gene expression in the anoxic zone in lung cancer are dilemmas. In the present study, a eukaryotic expression plasmid pUC57-HRE-JAB1 driven by a hypoxia response elements promoter was constructed and introduced into lung cancer cell line A549. The cells were then exposed to a chemotherapeutic drug cis-diamminedichloroplatinum (C-DDP). qRT-PCR and western blotting were used to determine the mRNA and protein level and flow cytometry to examine the cell cycle and apoptosis of A549 transfected pUC57-HRE-JAB1. The results showed that JAB1 gene in the A549 was overexpressed after the transfection, cell proliferation being arrested in G1 phase and the apoptosis ratio significantly increased. Importantly, introduction of pUC57-HRE-JAB1 significantly increased the chemotherapeutic sensitivity of A549 in an anoxic environment. In conclusion, JAB1 overexpression might provide a novel strategy to overcome chemotherapeutic resistance in lung cancer.

The Effect of Using Standing Step Condition on Biomechanical Variables during Jab in Boxing (복싱 잽(jab) 동작 시 제자리 스텝의 사용이 운동역학적 변인에 미치는 영향)

  • Lee, Seong-Yeol;Kwon, Moon-Seok
    • Journal of the Korean Applied Science and Technology
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    • v.37 no.2
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    • pp.232-240
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    • 2020
  • The purpose of this study was to analyze the effect of using standing step condition on biomechanical variables during jab in boxing. For this purpose, eight orthodox type college boxers(age = 20.38±0.52 yrs, height = 172.38±5.80 cm, body mass = 63.45±8.56 kg, career = 6.00±1.07 yrs) who without injury to the musculoskeletal system participated in the experiment over the last year. In order to verify the effect of biomechanical variables using standing step during jab in boxing, the paired t-test (α = .05) statistical method was used. First, W.S(with-step) showed a greater impact force than N.S(non-step), and muscle activity was analyzed to be low. Second, it was analyzed that the pelvis and foot segments move faster because W.S affects the velocity of the anterior segment of the human body. Third, the rotational movement of the pelvis was faster in W.S. Fourth, W.S was analyzed to have greater ground reaction force in the anterior caused by the right and left foot than N.S. Through this, it was found that the use of the standing step during jab increases the ground reaction force the velocity and rotational movement of the human segment. Therefore, it was confirmed that it allowed a faster and more agile movement, and thus produces a greater impact force with relatively less muscle activity. Therefore, in order to effectively deliver a greater impact force to the opponent during the jab, it was effectively analyzed to accompany the standing step.

Assessing the Precision of a Jackknife Estimator

  • Park, Daesu
    • Management Science and Financial Engineering
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    • v.9 no.1
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    • pp.1-10
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    • 2003
  • We introduce a new estimator of the uncertainty of a jackknife estimate of standard error: the jack-knife-after-jackknife (JAJ). Using Monte Carlo simulation, we assess the accuracy of the JAJ in a variety of settings defined by statistic of interest, data distribution, and sample size. For comparison, we also assess the accuracy of the jackknife-after-bootstrap (JAB) estimate of the uncertainty of a bootstrap standard error. We conclude that the JAJ provides a useful new supplement to Tukey's jackknife, and the combination of jackknife and JAJ provides a useful alternative to the combination of bootstrap and JAB.

Assessing the Precision of a Jackknife Estimator

  • Park, Dae-Su
    • Management Science and Financial Engineering
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    • v.9 no.1
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    • pp.4-10
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    • 2003
  • We introduce a new estimator of the uncertainty of a jackknife estimate of standard error: the jack-knife-after-jackknife (JAJ). Using Monte Carlo simulation, we assess the accuracy of the JAJ in a variety of settings defined by statistic of interest, data distribution, and sample size. For comparison, we also assess the accuracy of the jackknife-after-bootstrap (JAB) estimate of the uncertainty of a bootstrap standard error. We conclude that the JAJ provides a useful new supplement to Tukey's jackknife, and the combination of jackknife and JAJ provides a useful alternative to the combination of bootstrap and JAB.

A Study on the life of WooJam, Jang-Taegyung (우잠(愚岑) 장태경(張泰慶) 생애(生涯) 연구(硏究))

  • Park, Sang-Young;Lee, Jung-Hwa;Kwon, Oh-Min;Han, Chang-Hyun;Ahn, Sang-Woo
    • The Journal of Korean Medical History
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    • v.24 no.1
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    • pp.57-62
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    • 2011
  • With the discovery of WooJam JabJeo, Jang-Taegyung[1809~1887] was highlighted as a noted doctor who won fame in the neighborhood of Gwangju, but with 'WoodJam Mango' seeing the light of day, this study was able to confirm the appearance of a literary man enjoying a reputation enough to sway literary circles with his writing of poems. It's possible to confirm his past related to medical service only until age of 42, which is because description in "WooJam JabJeo" came to a halt there. The situation is that the contents of 'WooJam Mango' started from age of 46 and were carried on even until after his death by his followers. Therefore, there exists a very intense impression that he might have put a focus on the life as a literary man ever after his mid-40s. and considering that he breathed his last at the age of 79, it's not difficult for us to estimate that his life was predominantly a series of literary activities rather than a health care provider. The place names appearing in "WooJam JabJeo" and "WooJam Mango" are limited to today's Jeonlanam-do, and this researcher would say that the through-composed poems, which sang of the beauty of Gwangju area scenery are the works, deserve to get a spotlight in local history even today. Through the above discussion, this study could prove that WooJam is a flawless figure enough to represent Gwangju and Jeonlanam-do as a health care provider and a literary person as well.

The Effect of Health Behavior Practice and Jab Characteristics on Periodontal Disease of Employees (근로자의 건강행위실천과 직업특성이 치주질환에 미치는 영향)

  • Lee, Byung-Ho
    • Journal of the Korea Convergence Society
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    • v.9 no.11
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    • pp.145-152
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    • 2018
  • The purpose of this study was to reveal association between health behavior practice and jab characteristics on periodontal disease of employees. The analysis was conducted on 1,737 of above the age of nineteen in employees by using raw data from the 2015 National Health and Nutrition Survey. The data were analyzed using SPSS for windows version 24.0. Smoking, BMI and aerobic exercise in health behavior practice had statistically significant difference. Occupation, work status and regular work in jab characteristics had statistically significant difference. In conclusion, business owners need active management to health behavior practice their employees and the government needs to resolve the polarization of medical services through the development of oral health care policies for low-income people.