• Title/Summary/Keyword: nuclear export

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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.

UAP56- a key player with surprisingly diverse roles in pre-mRNA splicing and nuclear export

  • Shen, Hai-Hong
    • BMB Reports
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    • v.42 no.4
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    • pp.185-188
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    • 2009
  • Transcripts contain introns that are usually removed from premessenger RNA (MRNA) in the process of pre-mRNA splicing. After splicing, the mature RNA is exported from the nucleus to the cytoplasm. The splicing and export processes are coupled. UAP56 protein, which is ubiquitously present in organisms from yeasts to humans, is a DExD/H-box family RNA helicase that is an essential splicing factor with various functions in the prespliceosome assembly and mature spliceosome assembly. Collective evidence indicates that UAP56 has an essential role in mRNA nuclear export. This mini-review summarizes recent evidence for the role of UAP56 in pre-mRNA splicing and nuclear export.

CRM1 inhibitor S109 suppresses cell proliferation and induces cell cycle arrest in renal cancer cells

  • Liu, Xuejiao;Chong, Yulong;Liu, Huize;Han, Yan;Niu, Mingshan
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.2
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    • pp.161-168
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    • 2016
  • Abnormal localization of tumor suppressor proteins is a common feature of renal cancer. Nuclear export of these tumor suppressor proteins is mediated by chromosome region maintenance-1 (CRM1). Here, we investigated the antitumor effects of a novel reversible inhibitor of CRM1 on renal cancer cells. We found that S109 inhibits the CRM1-mediated nuclear export of RanBP1 and reduces protein levels of CRM1. Furthermore, the inhibitory effects of S109 on CRM1 is reversible. Our data demonstrated that S109 significantly inhibits proliferation and colony formation of renal cancer cells. Cell cycle assay showed that S109 induced G1-phase arrest, followed by the reduction of Cyclin D1 and increased expression of p53 and p21. We also found that S109 induces nuclear accumulation of tumor suppressor proteins, Foxo1 and p27. Most importantly, mutation of CRM1 at Cys528 position abolished the effects of S109. Taken together, our results indicate that CRM1 is a therapeutic target in renal cancer and the novel reversible CRM1 inhibitor S109 can act as a promising candidate for renal cancer therapy.

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.

Lights Out for South Korea's Nuclear Export Ambitions (세계의 창 - 대한민국 원전 수출의 불씨는 꺼지는가)

  • Nguyen, Viet Phuong
    • Nuclear industry
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    • v.37 no.8
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    • pp.21-23
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    • 2017
  • 최근까지 건실한 내수 시장 구축을 구축하고 수출 시장 일선에서 성과를 거둔 원자력산업의 성공 신화는 대한민국의 자부심이었다. 하지만 문재인 대통령의 탈원전 정책은 대한민국 원자력산업계의 전망을 어둡게 하고 있다. 이러한 정책은 대한민국 원자력산업계의 신뢰성와 역량, 그리고 가능성을 해치며 원전 기술 수출 가능성을 낮출 것이다. 탈원전 정책은 신고리 5,6호기 건설 중단에서 드러났듯이 대한민국 정부와 원전 사업자 간 혼란을 야기할 수 있다. 이러한 조건에서 러시아와 중국을 비롯한 강력한 경쟁자를 상대로 기존의 'Team Korea'가 보여주었던 탁월한 협력이 가능할지 의문이 들 수밖에 없다.

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An Analysis on the Trend of International Export control Regimes in Nuclear Industry (원자력산업에서 국제 수출통제 체제에 대한 동향 및 대응방안)

  • Ryu Jae-Su;Lee Byeong-Uk;Yang Maeng-Ho;Lee Han-Myeong
    • Proceedings of the Korea Technology Innovation Society Conference
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    • pp.203-212
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    • 2004
  • International nuclear export control regimes have been continuously strengthening through revision of guidelines to prevent a horizontal nuclear proliferation. Recently, they have been trying to include sensitive technologies, information exchange on export permission and supply conditions to their guidelines. Therefore, this study analyzes current issues of the amended guidelines within international export control regimes and proposes a proper solution to effectively implement the national regulation.

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Regulation of Nrf2-Mediated Phase II Detoxification and Anti-oxidant Genes

  • Keum, Young-Sam
    • Biomolecules & Therapeutics
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    • v.20 no.2
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    • pp.144-151
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    • 2012
  • The molecular mechanisms by which a variety of naturally-occurring dietary compounds exert chemopreventive effects have been a subject of intense scientific investigations. Induction of phase II detoxification and anti-oxidant enzymes through activation of Nrf2/ARE-dependent gene is recognized as one of the major cellular defense mechanisms against oxidative or xenobiotic stresses and currently represents a critical chemopreventive mechanism of action. In the present review, the functional significance of Keap1/Nrf2 protein module in regulating ARE-dependent phase II detoxification and anti-oxidant gene expression is discussed. The biochemical mechanisms underlying the phosphorylation and expression of Keap1/Nrf2 proteins that are controlled by the intracellular signaling kinases and ubiquitin-mediated E3 ligase system as well as control of nucleocytoplasmic translocation of Nrf2 by its innate nuclear export signal (NES) are described.