• 제목/요약/키워드: Activators

검색결과 345건 처리시간 0.029초

Tumor-Suppression Mechanisms of Protein Tyrosine Phosphatase O and Clinical Applications

  • Kang, Man-Man;Shan, Shun-Lin;Wen, Xu-Yang;Shan, Hu-Sheng;Wang, Zheng-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권15호
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    • pp.6215-6223
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    • 2015
  • Tyrosine phosphorylation plays an important role in regulating human physiological and pathological processes. Functional stabilization of tyrosine phosphorylation largely contributes to the balanced, coordinated regulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Research has revealed PTPs play an important suppressive role in carcinogenesis and progression by reversing oncoprotein functions. Receptor-type protein tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been identified to have some roles in tumor development. Some reports have shown PTPRO over-expression in tumors can not only inhibit the frequency of tumor cell division and induce tumor cell death, but also suppress migration. However, the tumor-suppression mechanisms are very complex and understanding is incomplete, which in some degree blocks the further development of PTPRO. Hence, in order to resolve this problem, we here have summarized research findings to draw meaningful conclusions. We found tumor-suppression mechanisms of PTPRO to be diverse, such as controlling G0/G1 of the tumor cell proliferation cycle, inhibiting substrate phosphorylation, down-regulating transcription activators and other activities. In clinical anticancer efforts, expression level of PTPRO in tumors can not only serve as a biomarker to monitor the prognosis of patients, but act as an epigenetic biomarker for noninvasive diagnosis. In addition, the re-activation of PTPRO in tumor tissues, not only can induce tumor volume reduction, but also enhance the susceptibility to chemotherapy drugs. So, we can propose that these research findings of PTPRO will not only support new study ideas and directions for other tumor-suppressors, importantly, but also supply a theoretical basis for researching new molecular targeting agents in the future.

Novel Dioxygenases, HIF-α Specific Prolyl-hydroxylase and Asparanginyl-hydroxylase: O2 Switch for Cell Survival

  • Park, Hyun-Sung
    • Toxicological Research
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    • 제24권2호
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    • pp.101-107
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    • 2008
  • Studies on hypoxia-signaling pathways have revealed novel Fe(II) and $\alpha$-ketoglutarate-dependent dioxygenases that hydroxylate prolyl or asparaginyl residues of a transactivator, Hypoxia-Inducible $Factor-\alpha(HIF-\alpha)$ protein. The recognition of these unprecedented dioxygenases has led to open a new paradigm that the hydroxylation mediates an instant post-translational modification of a protein in response to the changes in cellular concentrations of oxygen, reducing agents, or $\alpha$-ketoglutarate. Activity of $HIF-\alpha$ is repressed by two hydroxylases. One is $HIF-\alpha$ specific prolyl-hydroxylases, referred as prolyl-hydroxylase domain(PHD). The other is $HIF-\alpha$ specific asparaginyl-hydroxylase, referred as factor-inhibiting HIF-1(FIH-1). The facts (i) that many dioxygenases commonly use molecular oxygen and reducing agents during detoxification of xenobiotics, (ii) that detoxification reaction produces radicals and reactive oxygen species, and (iii) that activities of both PHD and FIH-1 are regulated by the changes in the balance between oxygen species and reducing agents, imply the possibility that the activity of $HIF-\alpha$ can be increased during detoxification process. The importance of $HIF-\alpha$ in cancer and ischemic diseases has been emphasized since its target genes mediate various hypoxic responses including angiogenesis, erythropoiesis, glycolysis, pH balance, metastasis, invasion and cell survival. Therefore, activators of PHDs and FIH-1 can be potential anticancer drugs which could reduce the activity of HIF, whereas inhibitors, for preventing ischemic diseases. This review highlights these novel dioxygenases, PHDs and FIH-1 as specific target against not only cancers but also ischemic diseases.

A Comparative Genome-Wide Analysis of GATA Transcription Factors in Fungi

  • Park, Jong-Sun;Kim, Hyo-Jeong;Kim, Soon-Ok;Kong, Sung-Hyung;Park, Jae-Jin;Kim, Se-Ryun;Han, Hyea-Young;Park, Bong-Soo;Jung, Kyong-Yong;Lee, Yong-Hwan
    • Genomics & Informatics
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    • 제4권4호
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    • pp.147-160
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    • 2006
  • GATA transcription factors are widespread eukaryotic regulators whose DNA-binding domain is a class IV zinc finger motif in the form $CX_{2}CX_{17-20}CX_{2}C$followed by a basic region. In fungi, they act as transcriptional activators or repressors in several different processes, ranging from nitrogen source utilization to mating-type switching. Using an in-house bioinformatics portal system, we surveyed 50 fungal and 9 out-group genomes and identified 396 putative fungal GATA transcription factors. The proportion of GATA transcription factors within a genome varied among taxonomic lineages. Subsequent analyses of phylogenetic relationships among the fungal GATA transcription factors, as well as a study of their domain architecture and gene structure, demonstrated high degrees of conservation in type IVa and type IVb zinc finger motifs and the existence of distinctive clusters at least at the level of subphylum. The SFH1 subgroup with a 20-residue loop was newly identified, in addition to six well-defined subgroups in the subphylum Pezizomycotina. Furthermore, a novel GATA motif with a 2f-residue loop ($CX_{2}CX_{21}CX_{2}C$, designated 'zinc finger type IVc') was discovered within the phylum Basidiomycota. Our results suggest that fungal GATA factors might have undergone multiple distinct modes of evolution resulting in diversified cellular modulation in fungi.

Conversion of C2C12 Myoblast into Adipoblast with Thiazolidinediones - A Possible Basis for Intramuscular Fat Generation in Meat Animals

  • Singh, N.K.;Chae, H.S.;Hwang, I.H.;Yoo, Y.M.;Ahn, C.N.;Lee, H.J.;Park, H.J.;Chung, H.Y.
    • Asian-Australasian Journal of Animal Sciences
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    • 제20권3호
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    • pp.432-439
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    • 2007
  • Thiazolidinediones (TZDs) act as potent activators of the adipose differentiation program in established preadipose cell lines. TZD's have also been investigated in diabetic patients and reported to act as PPAR-${\gamma}$ ligands. In this report, the effects of TZDs on the differentiation pathway of myoblasts have been investigated. C2C12 mouse myoblasts were grown in Dulbecco's Modified Eagles medium for 4-5 days until they reached almost 100% confluency. Post-confluent cells (day 0) were further exposed to adipogenic induction medium along with TZDs for 48 hours. Thereafter, cells were exposed only to TZDs every 48 h until day 10. The control was provided with differentiation medium without any treatment. Alterations in the cells during the differentiation programme were analyzed on the basis of fusion index, oil-red-o staining, adipocyte index, adipocyte stain uptake measurement, immuno-histochemistry and western blotting. Exposure of C2C12 mouse myoblasts to TZDs prevented the expression of myosin heavy chain with parallel increase in the expression of C/EBP-${\alpha}$ and PPAR-${\gamma}$ and acquisition of adipocyte morphology, thus abolishing the formation of multinucleated myotubes. TZDs exert their adipogenic effects only in non-terminally differentiated myoblasts; myotubes were insensitive to the compound. Continuous exposure (at least 4-5 doses) to inducers after the growth arrest was essential to provide a sustained environment to the cells converting to fully matured adipoctyes. The results indicate that TZDs specifically converted the differentiation pathway of myoblasts into that of adipoblasts.

Bradykinin-induced $Ca^{2+}$ signaling in human oral squamous cell carcinoma HSC-3 cells

  • Sohn, Byung-Jin;Kang, Ji-Ah;Jo, Su-Hyun;Choi, Se-Young
    • International Journal of Oral Biology
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    • 제34권2호
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    • pp.73-79
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    • 2009
  • Cytosolic $Ca^{2+}$ is an important regulator of tumor cell proliferation and metastasis. Recently, the strategy of blocking receptors and channels specific to certain cancer cell types has emerged as a potentially viable future treatment. Oral squamous cell carcinoma is an aggressive form of cancer with a high metastasis rate but the receptor-mechanisms involved in $Ca^{2+}$ signaling in these tumors have not yet been elucidated. In our present study, we report that bradykinin induces $Ca^{2+}$ signaling and its modulation in the human oral squamous carcinoma cell line, HSC-3. Bradykinin was found to increase the cytosolic $Ca^{2+}$ levels in a concentration-dependent manner. This increase was inhibited by pretreatment with the phospholipase C-${\beta}$ inhibitor, U73122, and also by 2-aminoethoxydiphenyl borate, an inhibitor of the inositol 1,4,5-trisphosphate receptor. Pretreatment with extracellular ATP also inhibited the peak bradykinin-induced $Ca^{2+}$ rise. In contrast, the ATP-induced rise in cytosolic $Ca^{2+}$ was not affected by pretreatment with bradykinin. Pretreatment of the cells with either forskolin or phorbol 12-myristate 13-acetate (activators of adenylyl cyclase and protein kinase C, respectively) prior to bradykinin application accelerated the recovery of cytosolic $Ca^{2+}$ to baseline levels. These data suggest that bradykinin receptors are functional in $Ca^{2+}$ signaling in HSC-3 cells and may therefore represent a future target in treatment strategies for human oral squamous cell carcinoma.

Genomic Organization of Penicillium chrysogenum chs4, a Class Ⅲ Chitin Synthase Gene

  • 박윤동;이명숙;남경준;박범찬;배경숙;박희문
    • 미생물학회지
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    • 제38권4호
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    • pp.230-230
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    • 2002
  • Class Ⅲ chitin synthases in filamentous fungi are important for hyphal growth and differentiation of several filamentous fungi. A genomic clone containing the full gene encoding Chs4, a class Ⅲ chitin synthase in Penicillium chrysogenum, was cloned by PCR screening and colony hybridization from the genomic library. Nucleotide sequence analysis and transcript mapping of chs4 revealed an open reading frame (ORF) that consisted of 5 exons and 4 introns and encoded a putative protein of 915 amino acids. Nucleotide sequence analysis of the 5′flanking region of the ORF revealed a potential TATA box and several binding sites for transcription activators. The putative transcription initiation site at -716 position was identified by primer extension and the expression of the chs4 during the vegetative growth was confirmed by Northern blot analysis. Amino acid sequence analysis of the Chs4 revealed at least 5 transmembrane helices and several sites for past-transnational modifications. Comparison of the amino acid sequence of Chs4 with those of other fungi showed a close relationship between P chrysogenum and genus Aspergillus.

Stleptomyces albus의 D-Xylose Isomerase의 성질에 관하여 (Characterization of D-Xylose Isomerase from Streptomyces albus)

  • 김영호;하영칠
    • 미생물학회지
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    • 제16권2호
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    • pp.47-61
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    • 1978
  • Strptomyces albus T-12 which ahd been isolated and identified in the laboratory, was selected for the studies on the cultural conditions on the production of D-xylose iosmerase and the enzymological characteristics using the partially purified enzyme. The best results in the enzyme production came from D-xylose medium than wheat bran. The divalent metla ions as $Co^{2+},\;Fe^{2+},\;Zn^{2+}\;and\;Cu^{2+}$ retard or inhibit the cell-growth at the early stages of mycelia propagations, and T-12 strain is especially sensitive to $Co^{2+}$. After 60 hours of shaking cultivation at $30^{\circ}C$ and 200 rpm, a maximum enzyme activitz, 0.49 enzyme units, was obtained. Cell-free enzyme obtained from mycelia heat-treated in the prescence of 0.5mM $Co^{2+}$, showed a 2.4-fold increase in specific than the enzyme from untreated mycelia. The specific activity of the purified enzyme through Sephadex G-150 columm showed 180 fold to the crude enzyme. The effective activators of the enzyme appeared to be $Mg^{2+}\;and\;Co^{2+}$ ions, and it exhibited the maximal enzyme activity showed at pH 7.0 and at tempersture around $80^{\circ}C$ when $Mg^{2+}\;and\;Co^{2+}$ ions were added. The enzyme isomerized D-glucose, D-xylose, D-ribose, L-arabinose, D-mannose, and L-rhamnose in the present of $Mg^{2+}\;and\;Co^{2+}$ ions as an activatiors. $Mg^{2+}\;and\;Co^{2+}$ ions were non-competitively bound at different allosterix sites of enzyme molecule. $Mg^{2+}(5mM)\;or\;Co^{2+}(1.0mM)$ protected against the thermal denaturations of the enzyme activities. The michelis constant(Km) and $V_{max}$ values of the emzyme for D-glucose and D-xylose were 0.52M, $2.12{\mu}moles/ml{\cdot}min.\;and\;0.28M,\;0.65moles/ml{\cdot}min.$, respectively.

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플라이애시 및 폴리실리콘 슬러지 혼입율에 따른 제지애시 경화체의 경량 특성 (Lightweight Properties of Matrix using Paper Ash according to Replacement Ratios of Fly Ash and Polysilicon Sludge)

  • 박선규;김윤미;이상수
    • 한국건설순환자원학회논문집
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    • 제2권2호
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    • pp.166-171
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    • 2014
  • 기포콘크리트의 재료 중 시멘트는 제조과정 중에 $CO_2$를 다량 발생시키기 때문에 지구 환경적인 측면에서 커다란 문제가 되고 있지만, 아직까지 시멘트를 대체할 수 있는 대체재에 대한 연구 개발이 미흡한 실정이다. 또한, 발포제는 압축강도가 낮고 고가인 단점이 있다. 이 때문에 강도와 경량 등의 성능 개선과 친환경적인 재료의 사용이 필요한 실정이다. 이에 본 연구에서는 시멘트와 발포제를 대체하기 위해 고로슬래그와 제지애시를 사용하여 경량 경화체를 제조하고자 하였으며, 강도 및 경량성을 보완하기 위해 플라이애시와 폴리실리콘 슬러지를 사용하여 실험을 실시하였다. 그 결과, 플라이애시를 사용한 경화체는 Plain 보다 낮은 밀도를 나타내었으나 강도보완에는 취약하였으며, 폴리실리콘 슬러지를 사용한 경우는 3%치환한 경화체가 압축강도는 Plain보다 다소 낮지만 겉보기 밀도의 감소가 큰 것으로 나타났다.

파파인 가공한 양모/폴리에스터 혼방직물의 정련 및 염색성 (Dyeing Properties and Scouring of Wool/Polyester Blend Fabrics Using Papain from Carica Papaya)

  • 송현주;김혜림;송화순
    • 한국의류학회지
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    • 제33권2호
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    • pp.213-221
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    • 2009
  • This study provides the optimum papain treatment method and its effect on wool/polyester blend fabrics. The enzymatic treatment condition is optimized depending on its pH level, temperature, concentration of enzyme, treatment time and concentration of activators. The characteristics of samples treated with the papain are measured using weight loss, tensile strength, whiteness, WCA, dyeing property and surface micrographs. The results are described as follows: According to measuring weight loss, tensile strength and whiteness, a pH level of 7.5, $70^{\circ}C$, 10% papain(o.w.f.) and 60minutes of treatment time are optimized for papain treatment. L-cysteine and sodium sulfite are able to activate the papain. The optimum concentrations of them are 10mM and 50mM respectively. The WCA of fabrics is decreased since papain treatment makes wool/polyester blend fabrics more hydrophilic. Scouring with papain treatment improves whiteness and dyeing property of fabrics. The dyeing property of papain-treated fabrics is enhanced simply by a single step dyeing process using a basic dye. The surface of wool treated with papain in the presence of L-cysteine shows to be descaled. The surface of wool fibers in the presence of sodium sulfite, however, shows it is hydrolyzed evenly instead of being descaled. The surface of papain treated polyester fibers shows cracks and voids.

Energy Transfer Fluorescence Quenching of $Pr^{3+}$ in LaOCI

  • Kim, Taesam;Ha, Younggu
    • 분석과학
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    • 제8권2호
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    • pp.125-129
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    • 1995
  • 두 가지 활성제를 분포시킨 LaOCl:Pr, Tb와 LaOCl:Pr, Eu계에서 에너지 전달을 관찰하였다. 레이저에 의한 들뜨기와 형광 스펙트럼의 관찰로부터 활성제 이온들 사이에 독특한 에너지 전달 과정이 있음을 발견하였다. $Tb^{3+}$에서 흡수한 에너지는 $Pr^{3+}$로 직접 전달되었다. 들뜬 $Pr^{3+}$의 에너지가 아래 준위인 $^1D_2$로 단계적으로 풀리는 현상이 $Eu^{3+}$에 의해 야기되었다. 비슷한 조건을 가진 $Tb^{3+}$$Eu^{3+}$처럼 촘촘한 $^7F_J$ 바닥 준위를 가지고 있으나 단계적 풀림에 효과적이지 못하였다. 이 결과는 에너지 전달에 있어서 이온의 양자 상태가 에너지 전달에 절대적인 조건이 되지 못하며 에너지 전달은 활성제가 가까이 있을 경우 그 준위들 사이에 경쟁적임을 보여 주었다.

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