• Title/Summary/Keyword: BH3 domain

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Cloning and Functional Studies of Pro-Apoptotic MCL-1ES BH3M (세포사멸을 유도하는 새로운 단백질인 MCL-1ES BH3M의 클로닝 및 기능연구)

  • Kim, Jae-Hong;Park, Mira;Ha, Hye-Jeong;Lee, Kangseok;Bae, Jeehyeon
    • Development and Reproduction
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    • v.12 no.3
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    • pp.297-303
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    • 2008
  • BCL-2 family members are essential protein for the regulation of cell death and survival consisting both antiapoptotic and pro-apoptotic proteins. In the present study, we designed and cloned a new apoptotic molecule MCL-1ES BH3M coding a modified protein of MCL-1L. Compared to MCL-1L protein, MCL-1ES BH3M lacks the PEST motifs known to be involved in MCL-1L protein degradation and has seven mutated residues in BH3 domain critical for dimerization with BCL-2 family members. Overexpression of MCL-1ES BH3M induced death of different cells, and its cell killing effect was not blocked by forced expression of the pro-survival protein MCL-1L. Expression of MCL-1ES BH3M protein led to the activation of caspase 9 and caspase 3, suggesting apoptotic cell death, and confocal fluorescent microscopic analyses showed that MCL-1ES BH3M was partially localized in mitochondria. In conclusion, we reported a new apoptotic molecule and determined its cell death activity in cells.

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Regulation of BNIP3 in Normal and Cancer Cells

  • Lee, Hayyoung;Paik, Sang-Gi
    • Molecules and Cells
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    • v.21 no.1
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    • pp.1-6
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    • 2006
  • Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is a mitochondrial pro-apoptotic protein that has a single Bcl-2 homology 3 (BH3) domain and a COOH-terminal transmembrane (TM) domain. Although it belongs to the Bcl-2 family and can heterodimerize with Bcl-2, its pro-apoptotic activity is distinct from those of other members of the Bcl-2 family. For example, cell death mediated by BNIP3 is independent of caspases and shows several characteristics of necrosis. Furthermore, the TM domain, but not the BH3 domain, is required for dimerization, mitochondrial targeting and pro-apoptotic activity. BNIP3 plays an important role in hypoxia-induced death of normal and malignant cells. Its expression is markedly increased in the hypoxic regions of some solid tumors and appears to be regulated by hypoxia-inducible factor (HIF), which binds to a site on the BNIP3 promoter. Silencing, followed by methylation, of the BNIP3 gene occurs in a significant proportion of cancer cases, especially in pancreatic cancers. BNIP3 also has a role in the death of cardiac myocytes in ischemia. Further studies of BNIP3 should provide insight into hypoxic cell death and may contribute to improved treatment of cancers and cardiovascular diseases.

Magenetic Properties of Nd-Fe-B-Co-based Melt-spun Ribbons an dTheir Bonded Magents (Nd-Fe-B-Co계 급냉리본과 Bond 자석의 자기적 성질)

  • Gang, Gye-Myeong;Gang, Gi-Won;O, Yeong-Min;Song, Jin-Tae
    • Korean Journal of Materials Research
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    • v.3 no.2
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    • pp.175-184
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    • 1993
  • Abstract Co-and/or AI-added Nd-Fe-B-based magnetic alloys were fabricated by using vacuum induction melting frunace, and melt-spun ribbons were made of the magnetic alloys with single roll rapid quenching method. The variation of magnetic properties of the melt-spun ribbons as a function of Cuwheel velocity (Vs) were investigated. Bonded magnets were made of the optimally quenched ribbon fragments, and the magnetic properties of the melt-spun ribbons and the bonded magnets were studied, relating to the microstructure and crystalline structure. Cu-wheel surface velocity had a strong effect on the magnetic properties of the melt-spun ribbons, and the maximum properties were obtained around Vs =20m/sec. The optimally quenched ribbon had a cellura-type microstructure, in which fine N$d_2$F$e_14$B grains were surrounded by thin Nd-rich phase. In case of a 2.1at% AI-added melt-spun ribbon, the magnetic properties were as follows: iHc, Br, and (BH)max were 15.5KOe, 7.8KG and 8.5MGOe respectively. And resin bonded magnets were fabricated by mixing optimally quenched ribbon fragments with 2.5wt % polyamide resin, compacting and binding at room temperature. The iHc, Br and (BH)max of bonded magnet were lO.2KOe, 4.4KG and 3.3MGOe respectively. And hot-pressed magnets were made by pressing the overquenched ribbons at high temperature. The magnetic properties of hot-pressed magnets were better than those of bonded magnets, and when the holding time was 8 minutes, the iHc, Br, and (BH)max of the hot-pressed magnet were 1O.8KOe, 7.3KG and 8.0MGOe respectively. Domain structure was mainly maze pattern, which means that the easy magnetization axis could be aligned, and the domain width of the hot-pressed magnets was smaller than that of bonded magnets.

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A study on the magnetic domain behaviors of the Fe-(Ce-Didymium)-B alloys (Fe-(Ce-Didymium)-B계 영구자석의 자구거동에 관한 연구)

  • 김종오
    • Electrical & Electronic Materials
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    • v.5 no.2
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    • pp.216-223
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    • 1992
  • 큰 보자력(iHc=19,500 Oe)과 큰에너지적[(BH)$_{max}$=32.50MGOe]을 갖는 Fe-(Ce-Didymium)-B 소결자석의 자구를 Bitter법을 개량한 Colloed SEM 법으로 관찰하였다. C축면의 자구는 소자상태에서 3-4.mu.m의 폭을 갖는 Stripe형이고 C축에 평행한 면은 미로형이다.

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The Role and Regulation of MCL-1 Proteins in Apoptosis Pathway

  • Bae, Jeehyeon
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2002.07a
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    • pp.113-113
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    • 2002
  • Phylogenetically conserved Bcl-2 family proteins play a pivotal role in the regulation of apoptosis from virus to human. Members of the Bcl-2 family consist of antiapoptotic proteins such as Bcl-2, Bcl-xL, and Bcl-w, and proapoptotic proteins such as BAD, Bax, BOD, and Bok. It has been proposed that anti- and proapoptotic Bcl-2 proteins regulate cell death by binding to each other and forming heterodimers. A delicate balance between anti- and proapoptotic Bcl-2 family members exists in each cell and the relative concentration of these two groups of proteins determines whether the cell survives or undergoes apoptosis. Mcl-1 (Myeloid cell :leukemia-1) is a member of the Bcl-2 family proteins and was originally cloned as a differentiation-induced early gene that was activated in the human myeloblastic leukemia cell line, ML-1 . Mcl-1 is expressed in a wide variety of tissues and cells including neoplastic ones. We recently identified a short splicing variant of Mcl-1 short (Mcl-IS) and designated the known Mcl-1 as Mcl-1 long (Mcl-lL). Mcl-lL protein exhibits antiapoptotic activity and possesses the BH (Bcl-2 homology) 1, BH2, BH3, and transmembrane (TM) domains found in related Bcl-2 proteins. In contrast, Mcl-1 S is a BH3 domain-only proapoptotic protein that heterodimerizes with Mcl-lL. Although both Mc1-lL and Mcl-lS proteins contain BH domains fecund in other Bcl-2 family proteins, they are distinguished by their unusually long N-terminal sequences containing PEST (proline, glutamic acid, serine, and threonine) motifs, four pairs of arginine residues, and alanine- and glycine-rich regions. In addition, the expression pattern of Mcl-1 protein is different from that of Bcl-2 suggesting a unique role (or Mcl-1 in apoptosis regulation. Tankyrasel (TRF1-interacting, ankyrin-related ADP-related polymerasel) was originally isolated based on its binding to TRF 1 (telomeric repeat binding factor-1) and contains the sterile alpha motif (SAM) module, 24 ankyrin (ANK) repeats, and the catalytic domain of poly(adenosine diphosphate-ribose) polymerase (PARP). Previous studies showed that tankyrasel promotes telomere elongation in human cells presumably by inhibiting TRFI though its poly(ADP-ribosyl)action by tankyrasel . In addition, tankyrasel poly(ADP-ribosyl)ates Insulin-responsive amino peptidase (IRAP), a resident protein of GLUT4 vesicles, and insulin stimulates the PARP activity of tankyrase1 through its phosphorylation by mitogen-activated protein kinase (MAPK). ADP-ribosylation is a posttranslational modification that usually results in a loss of protein activity presumably by enhancing protein turnover. However, little information is available regarding the physiological function(s) of tankyrase1 other than as a PARP enzyme. In the present study, we found tankyrasel as a specific-binding protein of Mcl-1 Overexpression of tankyrasel led to the inhibition of both the apoptotic activity of Mel-lS and the survival action of Mcl-lL in mammalian cells. Unlike other known tankyrasel-interacting proteins, tankyrasel did not poly(ADP-ribosyl)ate either of the Mcl-1 proteins despite its ability to decrease Mcl-1 proteins expression following coexpression. Therefore, this study provides a novel mechanism to regulate Mcl-1-modulated apoptosis in which tankyrasel downregulates the expression of Mcl-1 proteins without the involvement of its ADP-ribosylation activity.

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Identification of Bak-like Protein cDNA (Bak-like 단백질을 code하는 cDNA의 동정)

  • 김진경
    • YAKHAK HOEJI
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    • v.45 no.4
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    • pp.426-430
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    • 2001
  • Cells are eliminated in a variety of physiological settings by apoptosis, a genetically encoded process of cellular suicide. Bak, a member of the Bcl-2 protein family, accelerates apoptosis by an unknown mechanism. We have found a novel cDNA encoding a 101 amino acid protein possessing a Bak-like in our full-length cDNA bank. Bak-like shares the conserved domains BHI and 2 with other proapoptotic proteins but lacks the BH3 domain. Bak-like is expressed in a wide variety of tissues. Like Bak, Bak-like gene product primarily enhances apoptotic cell death following an appropriate stimulus.

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Mutational Analysis of Proapoptotic Bcl-2 Family Members in Gastric Carcinomas (위암에서의 고사유발성 Bcl-2 Family의 돌연변이에 관한 연구)

  • Yoo Nam Jin;Lee Jong Woo;Soung Young Hwa;Kim Hong Sug;Park Won Sang;Lee Jung Young;Lee Sug Hyung
    • Journal of Gastric Cancer
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    • v.3 no.2
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    • pp.84-87
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    • 2003
  • Purpose: Evidence exists that dysregulation of Bcl-2 family members is involved in the pathogenesis of cancer development. The aim of this study was to explore whether the somatic mutation of proapoptotic Bcl-2 member genes, one of the mechanisms that prolong the survival of cancer cells, is involved in gastric carcinogenesis. Materials and Methods: In the current study, to detect somatic mutations of the DNA sequences encoding the Bcl-2 homology 3 (BH3) domain of the human BAD, BIM, BIK, and Bcl-G genes in 60 advanced gastric adenocarcinomas, we used the polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP), and DNA sequencing. Results: The SSCP analysis revealed no mutations in the coding regions of the BH3 domain in the cancers. Conclusion: The data presented here indicate that proapoptotic Bcl-2 member genes, BAD, BIM, BIK, and Bcl-G, may not be mutated in human gastric carcinomas and suggest that these genes might be altered by mechanisms other mechanisms somatic mutation.

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Effects of Nd Addition to Sr Ferrite Bonded Magnet (Sr 페라이트 본드자석의 Nd 첨가효과)

  • 정왕일;진성빈;강재덕;신용진
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 1997.11a
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    • pp.120-123
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    • 1997
  • In this paper, we deal with the effect on magnetic properties when Nd is added to Sr ferrite bonded magnet. First, we choose SrO$_{n}$.Fe$_2$O$_3$(n=5.9), which is nonstoichiomatric composition, as specimen ferrite. Then, we add 5wt% polyvinyl alcohol and calcinate at 12$25^{\circ}C$ under $N_2$ environment for carbon coating on chemical compound specimen. After that we obtain 1.2${\mu}{\textrm}{m}$ single domain powder through grinding process for 18 hours. The single domain Sr ferrite Powder is well mixed with silage coupling and calcium stearate of 1wt% Then, it is kneaded by using polyamide12 as a binder and is pelleted. After adding Nd-Fe-B powder to the pelleted specimen, we injection-mould it under magnetic field by using anisotropic mould. Especially, when we add l3wt% Nd-Fe-B powder to the polyamide12, we obtain excellent magnetic propertiecs which are $_{B}$H$_{C}$=2.65KOe, Br=3.16KG and (BH)$_{max}$=2.61MGOeOeOeOeOe

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A Study on the Fabrication for High Quality Ferrite Plastic Magnets (고품위 페라이트 본드자석 제조에 관한 연구)

  • 신용진;문형욱;진성빈;정왕일
    • Electrical & Electronic Materials
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    • v.10 no.5
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    • pp.440-446
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    • 1997
  • This research has been performed for the fabrication of high quality ferrite plastic magnet. The magnetic properties of S $r_{5.9}$F $e_2$ $O_3$ ferrite bonded magnets by injection moulding with a variety of applied magnetic field were investigated. 0.3wt% CaCO3, 0.2wt% $SiO_2$, 0.5wt% $Al_2$ $O_3$and 0.5wt% N $a_2$ $SiO_3$are added in order to improve the magnetic properties of Sr-ferrite plastic magnets during the powder fabrication. For carbon coating on chemical compound specimen, 5wt% polyvinyl alcohol is added, and then calcinated under $N_2$ environment of 12$25^{\circ}C$. The particle size is distributed from 0.9~1.2${\mu}{\textrm}{m}$ which approximates to the single domain. The obtained Sr ferrite powder is well mixed with silane coupling and calcium stearate of 1wt%. Nest, the specimen is pelleted after kneading each of them with polyamidel2 as a binder. When the temperature of injection and mould were 25$0^{\circ}C$ and 8$0^{\circ}C$ respectively at injection pressure of 200kgf/$\textrm{cm}^2$, the degree of orientation was 85.3% under the applied magnetic field of 12kOe. As the results, when the packing density of Sr ferrite powder was 90wt%, the magnetic properties of Sr ferrite bonded magnet were follows : $_{B}$ $H_{c}$=2.41kOe, Br=3.1kG, (BH)$_{max}$=2.21MgOe. Especially, the Sr-ferrite bonded magnet with 10wt% N $d_2$F $e_{14}$B additive were as follows : $_{B}$ $H_{c}$=2.57kOe, Br=3.14kG and (BH)$_{max}$=2.39MGOe.GOe.GOe.GOe.e.

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A study on the magnetic properties of (Ce-Didymium)-Fe-B alloy ((Ce-Didymium)-Fe-B 합금의 자기적 성질에 관한 연구)

  • 김종오;노재승
    • Electrical & Electronic Materials
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    • v.3 no.1
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    • pp.36-44
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    • 1990
  • 본 연구는 34wt%(5Ce-Didymium)-Fe-1wt%B 합금의 분말입도, 성형압력 및 소결온도 에 따른 자기적 성질에 관하여 연구하였다. 그리고 각각의 자기적 성질에 영향을 주는 인자를 알아내기 위하여 밀도측정, 미세조직 및 자구를 관찰하였다. 미세조직은 금속현미경을 이용하여 관찰하였으며 자구는 Bitter법으로 관찰하였다. 결과는 아래와 같다. (1)분말의 입도와 결정립 크기가 작아질수록 경질자기 특성은 증가하였으며 소결온도가 증가할수록 경질자기 특성도 증가하였다. 그러자 압력은 1000kg/$cm^{2}$일때 가장 좋은 경질자기 특성이 얻어졌다. (2)결정립이 클수록 자구의 구조는 복잡했으며 미세한 결정립일수록 큰 결정립에 비해 큰 보자력을 갖는다. 포화된 후에는 거의 모든 결정립이 단자구였으며 열적으로 탈자되었을 경우에는 모두가 multi-domain였다. (3)가장 우수한 경질자기 특성은 3-5.mu.m의 분말을 사용하여 1080.deg.C에서 소결한 후 590.deg.C에서 열처리한 시편에서 얻어졌으며 (BH)$_{max}$는 214.6kJ.m$_{-3}$이다.

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