96,589 research outputs found
C/EBPalpha downregualtes c-jun expression
No full textThe transcription factor C/EBPa is crucial for the differentiation of granulocytes. Conditional expression of C/EBPa triggers neutrophilic differentiation and C/EBPa can block TPA induced monocytic differentiation of bipotential myeloid cells. In C/EBPa knockout mice, no mature granulocytes are present. A dramatic increase of c-jun mRNA in C/EBPa knockout mice fetal liver was observed. c-jun, a component of the AP-1 transcription factor complex and a co-activator of the transcription factor PU.1, is important for monocytic differentiation. Here we report that C/EBPa downregulates c-jun expression to drive granulocytic differentiation. Ectopic increase of C/EBPa expression decreases c-jun mRNA level, and the human c-jun promoter activity is downregulated 8 fold in presence of C/EBPa. C/EBPa and c-jun interact through their leucine zipper domains and this interaction prevents c-jun from binding to DNA. This results in downregulation of c-jun’s capacity to autoregulate its own promoter through the proximal AP-1 site. Overexpression of c-jun prevents C/EBPa induced granulocytic differentiation. c-jun expression was higher in AML M2 patients with dominant negative C/EBPa mutations in comparison to AML M2 patients without C/EBPa mutations. Thus, we propose a model in which C/EBPa needs to downregulate c-jun expression and transactivation capacity for promoting granulocytic differentiation.Der Transkriptionsfaktor C/EBPa ist essentiell für die Differenzierung von Granulozyten. Die konditionelle Expression von C/EBPa induziert die neutrophile Differenzierung. Überdies kann C/EBPa die TPA-induzierte Differenzierung von myeloiden Vorläuferzellen zu Monozyten blockieren. In C/EBPa knockout Mäusen gibt es keine reifen Granulozyten. In der fötalen Leber von C/EBPa knockout Mäusen konnte eine stark erhöhte Expression der c-jun mRNA beobachtet werden. c-jun ist eine Komponente des AP-1 Transkriptionsfaktorkomplexes, ein Koaktivator des Transkriptionsfaktors PU.1 und ist wichtig für die Differenzierung von Monozyten. In dieser Arbeit zeigen wir, dass C/EBPa die c-jun Expression herunterreguliert und somit die Differenzierung von Granulozyten induziert. Die Überexpression von C/EBPa reduzierte die c-jun mRNA Menge und die Aktivität des humanen c-jun Promotors war in der Gegenwart von C/EBPa 8-fach herunterreguliert. C/EBPa und c-jun interagieren über ihre Leucin-Zipper Domänen und diese Interaktion verhindert die DNA-Bindung von c-jun. Dies resultiert in einer verminderten Kapazität von c-jun, den eigenen Promotor über die proximale AP-1 Stelle zu regulieren. Die Überexpression von c-jun blockiert die durch C/EBPa induzierte granulozytäre Differenzierung. Die c-jun Expression war in AML-M2 Patienten mit dominant-negativen Mutationen in C/EBPa im Vergleich zu AML-M2 Patienten ohne Mutationen in C/EBPa erhöht. Aufgrund dieser Daten schlagen wir ein Modell vor, in dem C/EBPa die Expression und Transaktivierungskapazität von c-jun herunterregulieren muß, um die granulozytäre Differenzierung zu induzieren
Signaling through CD44 affects cell cycle progression and c-Jun expression in acute myeloid leukemia cells
No full textWe present here the first evidence linking CD44 signaling to c-Jun expression and cell cycle progression in myeloid cell line models. CD44 ligation with the anti-CD44 monoclonal antibodies have been shown to induce differentiation and inhibit the proliferation of human acute myeloid leukemia (AML) cells, and c-Jun is involved in the regulation of these processes. The effects of anti-CD44 monoclonal antibody A3D8, on myeloid cells were associated with specific disruption of cell cycle events and induction of G0/G1 arrest. Induction of G0/G1 arrest was accompanied by an increase in the expression of p21, attenuation of pRb phosphorylation and associated with decreased CDK2 and CDK4 kinase activities. We observed that A3D8 treatment of AML patient blasts and HL60/U937 cells led to the downregulation of c-Jun expression at mRNA and protein level. Transient transfection studies showed the inhibition of c-jun promoter activity by A3D8, involving both AP-1 sites. Furthermore, A3D8 treatment caused a decrease in JNK protein expression and a decrease in the level of phosphorylated c-Jun. Ectopic overexpression of c-Jun in HL60 cells was able to induce proliferation and prevent the anti-proliferative effects of A3D8. Targeting of G1 regulatory proteins and the resulting induction of G1 arrest by A3D8 may provide new insights into anti-proliferative and differentiation therapy of AML
Proto-oncogene c-jun expression is induced by AML1-ETO in a JNK dependent manner:possible role in the pathogenesis of acute myeloid leukemia
No full textOverexpression of proto-oncogene c-jun and constitutive activation of the Jun NH2-terminal kinase (JNK) signaling pathway have been implicated in the leukemic transformation process. However, c-jun expression has not been investigated in acute myeloid leukemia (AML) cells containing the most common chromosomal translocations. t(8;21) is one of the most common AML-associated translocation and results in the AML1-ETO fusion protein. Overexpression of AML1-ETO in NIH3T3 cells leads to increased phosphorylation of Ser63 in c-Jun, which is generally JNK dependent. The role of the JNK signaling pathway for the functional properties of AML1-ETO is, however, unknown.
In the present study we found high expression levels of c-jun mRNA in t(8;21), t(15;17) or inv(16) positive patient cells by microarray analysis. Within t(8;21) positive patient samples, there was a correlation between AML1-ETO and c-jun mRNA expression levels. In myeloid U937 cells, c-jun mRNA and c-Jun protein expression levels increased upon induction of AML1-ETO. AML1-ETO transactivated the human c-jun promoter through the proximal AP-1 site via activating the JNK signaling pathway. JNK targets c-Jun and ATF-2, which also bind to the proximal AP-1 site in U937 cells, were also phosphorylated upon AML1-ETO induction. Furthermore, AML1-ETO induction increased the DNA binding capacity of c-Jun and ATF-2 to the proximal AP-1 site of the c-jun promoter, which might result in their enhanced transactivation capacities.
Interference with JNK and c-Jun activation by using JIP-1 or a JNK inhibitor reduced the transactivation capacity of AML1-ETO on the c-jun promoter and the pro-apoptotic function of AML1-ETO in U937 cells. AML1-ETO seems to activate the JNK signaling pathway by inducing the expression of a cytoplasmic factor, possibly G-CSF, because supernatant of AML1-ETO expressing cells was sufficient to induce phosphorylation of JNK and c-Jun in wildtype U937 cells.
This data demonstrates a novel mechanism of how AML1-ETO might exert positive effects on target gene expression and identifies the proto-oncogene c-jun as a common target gene in AML patient cells.Überexpression des Proto-Onkogens c-jun und konstitutive Aktivierung des Jun NH2-terminalen Kinase (JNK)-Signaltransduktionsweges sind wichtig für die leukämische Transformation in der Chronischen Myeloischen Leukämie. Die Expression von c-jun bei Akuter Myeloischer Leukämie (AML) mit den häufigsten reziproken Translokationen ist jedoch unbekannt. Bei einer der häufigsten AML Translokation t(8;21) wurde in Fibroblastenzellen gezeigt, daß das AML1-ETO-Fusionsgen die Phosphorylierung des Serin 63 in c-Jun erhöht. Die Rolle des JNK-Signalweges, der c-Jun am Serin 63 phosphorylieren kann, für die Funktion von AML1-ETO wurde bisher jedoch nicht untersucht. Weiterhin kann aktiviertes c-Jun durch eine positive Rückkoppelungsschleife über den c-jun Promotor zur Erhöhung der c-Jun Expression führen.
In der vorliegenden Arbeit konnten wir zeigen, daß AML Patientenzellen mit den häufigen Translokationen: t(8;21), t(15;17) oder inv(16) mehr c-jun mRNA besitzen im Vergleich zu Knochenmarkszellen gesunder Probanden. Weiterhin fanden wir eine hohe Korrelation zwischen der AML1-ETO und der c-jun mRNA bei t(8;21) positiven Patientenzellen. Induktion von AML1-ETO in der myeloischen U937 Zellinie erhöhte sowohl c-jun mRNA als auch c-Jun Proteinexpression. Damit konnten wir zeigen, daß AML1-ETO die Erhöhung der c-jun Expression bewirkt. Wir untersuchten den molekularen Mechanismus in U937 Zellen mittels transienter Transfektionen und fanden, daß AML1-ETO den c-jun Promotor durch die proximale AP-1 Seite transaktiviert. Diese Transaktivierung erfolgte indirekt über Aktivierung des JNK-Signaltransduktionsweges durch AML1-ETO. AML1-ETO-Induktion führte auch zur Phosphorylierung der JNK-Zielproteine c-Jun und ATF-2. Diese konnten im Gelretardierungsassay an die proximale AP-1 Seite des c-jun Promotors binden und wurden durch AML1-ETO-Induktion in ihrer Bindungsfähigkeit verstärkt. Deshalb nehmen wir an, daß die Transaktivierungskapazität des c-jun Promotors durch AML1-ETO über die Aktivierung des JNK-Signalweges läuft
Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene
No full textG protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH beta-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH2-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH beta-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH2-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH beta-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression
Transforming growth factor beta (TGF beta) mediates schwann cell death in vitro and in vivo: Examination of c-jun activation, interactions with survival signals, and the relationship of TGF beta-mediated death to schwann cell differentiation
No full textIn some situations, cell death in the nervous system is controlled by an interplay between survival factors and negative survival signals that actively induce apoptosis. The present work indicates that the survival of Schwann cells is regulated by such a dual mechanism involving the negative survival signal transforming growth factor beta (TGF beta), a family of growth factors that is present in the Schwann cells themselves. We analyze the interactions between this putative autocrine death signal and previously defined paracrine and autocrine survival signals and show that expression of a dominant negative c-Jun inhibits TGF beta -induced apoptosis. This and other findings pinpoint activation of c-Jun as a key downstream event in TGF beta -induced Schwann cell death. The ability of TGF beta to kill Schwann cells, like normal Schwann cell death in vivo, is under a strong developmental regulation, and we show that the decreasing ability of TGF beta to kill older cells is attributable to a decreasing ability of TGF beta to phosphorylate c-Jun in more differentiated cells
Enhanced vertical photo-sensitivity in mu c-Si : H/a-Si : H superlattices
No full textThe microcrystalline silicon/amorphous silicon (mu c-Si:H/a-Si:H) superlattice showed an enhanced vertical,photo- sensitivity (photo-conductivity/dark-conductivity), whereas it reserved a lateral photo-sensitivity nearly unchanged. The film was fabricated by alternating the mixing of SiH4 and HZ in a photo-chemical vapor deposition system. The fact that a high vertical photo-sensitivity and an obvious crystalline volume fraction can be obtained at the same time distinguishes the mu c-Si:H/a-Si:H superlattice from the bulk mu c-Si:H. The change of the vertical dark-conductivity with the sublayer thickness was explained by the change of the a-Si:PI sublayer's electrical conduction property. We think that the thin a-Si:H sublayers play an important role of perturbing a columnar structure of the mu c-Si:H. (C) 2000 Elsevier Science B.V. All rights reserved
Low Degradation and High Annealing Effects of Amorphous Silicon Multilayer Processed through Alternate Hydrogen Dilution
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VHF 유도 결합 플라즈마 원 개발 및 플라즈마 변수들의 주파수 효과에 관한 연구
No full text학위논문(박사) - 한국과학기술원 : 물리학과, 2009.2, [ vii, 95 p. ]A large-area inductively coupled plasma (ICP) source capable of securing azimuthal plasma uniformity at a 40.00 MHz has been developed. The antenna, referred to as a capacitor distributed resonance antenna, minimizes the azimuthally non-uniform antenna capacitive field with eight distributed vertical capacitors. The antenna was designed to maximize the antenna current using L-C series resonance. Based on plasma diagnostics with a 13.56 MHz conventional ICP, comparative analyses were performed in terms of the plasma density, electron temperature, and frequency characteristics of the electron energy probability function (EEPF). In addition, the frequency dependency of the EEPF was found in the collisional ( > ω), normal skin () regime and the physical causes were examined. Also, a cooling mechanism for bulk electrons, according to increased capacitive coupling, was discovered in a high frequency discharge using inductively coupled plasma. It was found that when antenna voltage increases by high frequency driving, the threshold energy required for wall loss in the sheath collapse phase decreases, and electrons with lower energy can participate in the wall loss. This expansion of the depletion range for high energy electrons decreases the effective temperature for bulk electrons. To confirm this, we carried out Electron Energy Probability Function (EEPF) measurement and particle-in-cell (PIC) simulation according to increased driving frequency.한국과학기술원 : 물리학과
Erbium-doped fiber ring laser characterization for the application of multi-wavelength light source
No full text학위논문(석사) - 한국과학기술원 : 물리학과, 2007, [ iii, 52 p. ]본 논문에서는 다파장 발진 광원을 만들기 위한 선행 연구로서, EDF의 기본적인 이득 특성들과 EDF 원형 레이저의 발진 형태를 살펴보았다.
펌핑의 세기나 신호광 등 외부 변수에 관계없는 EDF의 고유한 특성값으로는 흡수 계수, 이득계수 그리고 포화 출력을 들 수 있다. 이외 EDF의 길이, 펌핑광의 세기 등은 원하는 출력 범위에 따라 최적화를 해주어야 낭비되는 EDF 성분이 없고 펌프광의 bleaching 현상 등을 막을 수 있다. 본 실험에서는 1525~1560nm 파장에 대해 흡수 계수를 측정하였고, 이득 계수를 측정하기 위해 입력 신호광, 펌프광에 따른 이득을 측정하여 small-signal regime을 검증해 보았다. 이에 따라 -30dBm의 입력광으로 EDF 길이에 걸쳐 균일한 펌핑이 되도록 펌프광의 세기를 주어 1525~1560nm 파장에 대해 이득 계수를 측정할 수 있었다. 포화 출력 또한 펌핑광이 없는 상태에서 측정하여 계산하였고, 포화 변수(parameter) 값을 계산해 보았다. EDFA나 EDF 원형 레이저에서는 레이저광의 진행 방향에 대한 펌프광의 방향이 중요한 역할을 한다는 것을 실험적으로 측정해 볼 수 있었다. 펌프광이 레이저광 방향에 대해 순방향으로 가해질 경우, EDF의 길이가 최적화되어 있지 않으면 펌프광이 EDF의 앞부분에서 모두 밀도반전에 소모되어 EDF 뒷부분은 흡수체 역할을 하게 된다. 따라서 흡수계수가 제일 큰 1530nm 파장대는 큰 흡수 손실을 겪게 되어 증폭이나 레이저 발진이 거의 되지 않음을 확인할 수 있었다. 따라서 역방향 펌핑이 더 안전하고 안정적이라고 할 수 있다. 하지만 EDF 원형 레이저의 경우에는 결국 EDF 길이가 최적화되어 있지 않으면 매 회전후 EDF 앞부분에서 또한 흡수 손실을 겪에 되므로 EDF 길이, 펌프광 세기 등 주요 파라미터들의 최적화가 반드시 필요하다고 할 수 있겠다.
본 실험에서는 EDF의 길이를 최적화하는 실험은 진행하지 못하였으나 이후 본격적인 다파장 발진 광원 구성을 위해서 추후 실험을 진행할 예정이다.
EDF 원형 레이저의 발진 특성 또한 EDF 길이, 펌프광의 세기, 펌프광의 방향 등에 따라 살펴보았다. 그리고 FPF를 결합하여 0.76nm 간격의 파장들이 얻어짐을 확인하였다. 하지만 EDF의 homogeneous broadening 때문에 좁은 파장대역에서 주로 이득이 발생하고 이득 경쟁 또한 매우 심한 것을 알 수 있었다. 따라서 이후 목표로 하고 있는 넓은 파장 영역에서 다파장 발진을 위해서는 이를 해결하는 방법이 필요하다. 가능한 접근 방법들로는, 1) EDF가 원형 레이저에서 공진하면서 inhomogeneous loss를 겪도록 하여 이득을 평탄화할 경우 넓은 파장에 걸쳐 다파장 발진을 할 수 있다. 2) 모드록킹된 EDF 원형 레이저를 꾸밀 경우 발진 종모드들 간에 서로 결맞아 있어 각 모드별로 분리했을 경우 주변 모드를 가지지 않는다. 이 때 분리된 모드들이 분산이나 비선형 과정을 겪게 되면 주변 모드가 생겨날 수 있으므로 이러한 과정을 배제해 준다. 3) SOA, LOA 등의 inhomogeneous broadening 하는 소자를 이용하여 레이저를 구성할 경우 우선 레이저에서 발진되는 모드 간에 서로 상관관계가 작아 각 모드로 분리해도 주변 모드를 가질 가능성이 적다. 이후에는 이러한 접근방법들을 시뮬레이션과 실험을 통해 다파장 발진을 이루고자 한다. 그리고 한 채널당 분리하여 주변 모드 특성을 살펴본 후 더 나은 개념을 찾도록 할 예정이다.한국과학기술원 : 물리학과
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