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MiR-21 Mediates the Radiation Resistance of Glioblastoma Cells by Regulating PDCD4 and hMSH2 被引量:5
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作者 晁腾飞 熊慧华 +2 位作者 刘巍 陈阳 张佳璇 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2013年第4期525-529,共5页
Summary: The purpose of this study was to investigate the molecular mechanism by which miR-21 and its target genes mediate radiation resistance of glioblastoma cells. Real-time PCR was employed to detect miR-21 expre... Summary: The purpose of this study was to investigate the molecular mechanism by which miR-21 and its target genes mediate radiation resistance of glioblastoma cells. Real-time PCR was employed to detect miR-21 expression in normal brain tissues, glioblastoma tissues and glioblastoma cell lines (A172, T98G and U87MG). T98G cells were transfected with anti-miR-21 oligonucleotides, or plasmids con- taining PDCD4 or hMSH2 (PDCD4-pcDNA3 and hMSH2-pcDNA3). The survival curve was obtained to investigate the sensitivity of T98G cells to radiation. Cell apoptosis was measured by using the Cas- pase-3/7 kit and cell cycle by flow cytometry. Western blotting was performed to detect the expression of hMSH2 and PDCD4 in miR-21-inhibiting T98G cells. The results showed that miR-21 expression in glioblastoma cells and tissues was conversely associated with the radiation sensitivity. Over-expression of miR-21 resulted in radiation resistance, while knockdown of miR-21 led to higher sensitivity of glioblastma cells to radiation. After miR-21 knockdown, the apoptosis of T98G cells was significantly increased and the G2 phase arrest was more significant. In addition, miR-21 knockdown increased the expression of endogenous PDCD4 and hMSH2, which contributed to the apoptosis and G2 arrest of T98G cells. The findings suggested that miR-21 may mediate the resistance of glioblastoma cells against radiation via its target genes PDCD4 and hMSH2. MiR-21 and its target genes may be used as potential molecular targets for clinical radiotherapy sensitization in the future. 展开更多
关键词 microRNA GLIOBLASTOMA radiation resistance apoptosis cell cycle
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Radiation Resistance of Fluorine-Implanted PNP Using Gated-Controlled Lateral PNP Transistor Structure 被引量:1
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作者 王信 陆妩 +6 位作者 马武英 郭旗 王志宽 何承发 刘默寒 李小龙 贾金成 《Chinese Physics Letters》 SCIE CAS CSCD 2016年第8期85-87,共3页
The radiation damage responses of ttuorinated and non-fluorinated lateral PNP transistors are studied with specially designed gated-controlled lateral PNP transistors that allow for the extraction of the oxide trapped... The radiation damage responses of ttuorinated and non-fluorinated lateral PNP transistors are studied with specially designed gated-controlled lateral PNP transistors that allow for the extraction of the oxide trapped charge (Not) and interface trap (Nit) densities. All the samples are exposed in the Co-60γ ray with the dose rate of 0.5 Gy(Si)/s. After the irradiation, the buildup of Not and Nit of the samples with total dose is investigated by the gate sweep test technique. The results show that the radiation resistance of fluorinated lateral PNP transistors is significantly enhanced compared with the non-fluorinated ones. 展开更多
关键词 of in is on PNP radiation resistance of Fluorine-Implanted PNP Using Gated-Controlled Lateral PNP Transistor Structure
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Radiation resistance property of barium gallo-germanate glass doped by Nb_(2)O_(5)
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作者 刘桂榕 陈晓东 +5 位作者 刘红刚 王琰 孙敏 闫娜 钱奇 杨中民 《Chinese Physics B》 SCIE EI CAS CSCD 2022年第2期593-597,共5页
Effects of Nb_(2)O_(5)dopant on the radiation response of barium gallo-germanate(BGG)glass are studied mainly by electron paramagnetic resonance and absorption spectroscopy.Owing to the Nb^(5+)$Nb^(3+)interconversion ... Effects of Nb_(2)O_(5)dopant on the radiation response of barium gallo-germanate(BGG)glass are studied mainly by electron paramagnetic resonance and absorption spectroscopy.Owing to the Nb^(5+)$Nb^(3+)interconversion in doped samples,formations of Ge-related non-bridging oxygen hole center and Ge-related electron center defects after g-ray irradiation are inhibited.Thereby,Nb_(2)O_(5)dopant can enhance radiation resistance of BGG glass,and 1.0%Nb2O5 concentration is the best. 展开更多
关键词 germanate glass radiation resistance Nb2O5 dopant
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Optimization of Extraction Conditions for Total Flavonoids from Fructus Aurantii Immaturus and Its Anti-UVB Radiation Activity
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作者 Xu CHANG Yanhui WANG +5 位作者 Ximing LIU Yunge MA Yunhao LIU Xiaobo CHEN Mengyao SUN Liyan LI 《Agricultural Biotechnology》 CAS 2023年第4期110-114,118,共6页
[Objectives]Optimum extraction conditions of total flavonoids from Fructus Aurantii Immaturus(TFFAI)and its resistance activity to ultraviolet radiation were investigated in present research.[Methods]The optimal extra... [Objectives]Optimum extraction conditions of total flavonoids from Fructus Aurantii Immaturus(TFFAI)and its resistance activity to ultraviolet radiation were investigated in present research.[Methods]The optimal extraction conditions of TFFAI were determined by single factor and orthogonal experiments,and the survival rate of TFFAI on HaCaT cells irradiated with UVB rays was investigated.It s antioxidant capacity was determined by ABTS.[Results]The results showed that the highest yield of TFFAI was obtained with 70%ethanol at a solid-to-liquid ratio of 1:50(w/v)and 40℃for 1.5 h by single-factor and orthogonal experiments.Total flavonoids(0.25-1.00 mg/ml)could significantly improve the survival rate of HaCaT cell line.Meanwhile,the maximum absorption peak of TFFAI was found at 283 nm,and in-vitro antioxidant experiment identified that TFFAI had a good clearance rate to ABTS.It suggestes that TFFAI could protect the cells from UVB damage by absorption of UVB rays and anti-oxidation.[Conclusions]TFFAI played a protective role on UVB irradiated cells through UVB ultraviolet absorption and antioxidant pathways. 展开更多
关键词 Fructus Aurantss Immaturus Total flavonoids Optimization of extraction conditions UVB radiation resistance
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The Effects by γ Ray Irradiation on Silicon Photodiodes
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作者 Chen Bingruo Huang Qijun +5 位作者 Li Shiqing Yan Heping Gao Fanrong Tang Chenghuan Xian Meizhi Yin Deqiang 《Wuhan University Journal of Natural Sciences》 CAS 1996年第1期62-66,共5页
The relationships between irradiation doses of γ ray and the main photoelectric characteristics of PIN photodiode or conventional photodiode with different structure were studied. The experimental results show that a... The relationships between irradiation doses of γ ray and the main photoelectric characteristics of PIN photodiode or conventional photodiode with different structure were studied. The experimental results show that after the photodiodes being irradiated,the photocurrent decreases,especially for short wavelength of light. The dark current of the photodiodes with smaller active area decreases while increases for that with larger active area,and the response time shortens. The plane scanning experiment of laser beam indicates that the homogeneity of the device's surface is not influenced by the irradiation. The results prove that PIN photodiode shows relatively good radioresistance. 展开更多
关键词 ?irradiation photoelectric characteristics PIN photodiode conventional photodiode radiation resistance
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Charged particles:Unique tools to study irradiation resistance of concentrated solid solution alloys
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作者 Yanwen Zhang Lumin Wang William J.Weber 《Journal of Materials Science & Technology》 SCIE EI CAS CSCD 2023年第9期260-276,共17页
Many multicomponent concentrated solid solution alloys(CSAs),including high-entropy alloys(HEAs),exhibit improved radiation resistance and enhanced structural stability in harsh environments.To study and assess irradi... Many multicomponent concentrated solid solution alloys(CSAs),including high-entropy alloys(HEAs),exhibit improved radiation resistance and enhanced structural stability in harsh environments.To study and assess irradiation resistance of nuclear materials,energetic ion and electron beams are commonly used to create displacement damage.Moreover,charged particles of ions,electrons,and positrons are unique tools to create and characterize radiation effects.Ion beam analysis(e.g.,Rutherford backscattering spectrometry,nuclear reaction analysis,and time-of-flight elastic recoil detection analysis),electron microscopy techniques(e.g.,transmission or scanning electron microscopy,and electron diffraction),and positron annihilation spectroscopy have been applied to characterize irradiated CSAs or HEAs to understand defect formation and evolution together with chemical and microstructural information.Their distinctive analyzing power and some perspectives in these techniques are reviewed.In developing structural alloys desirable for applications in advanced reactors,neutron exposure is a critical test but the limitation in achievable high damage levels is,however,a bottleneck.Ion irradiation is often used as a surrogate for neutron irradiation,and the associated reduced transmutations and higher displacements per atom(dpa)rates are desirable for materials research.Nevertheless,cautions need to be taken when relying on ion irradiation results for reactor evaluations.Literature on differences between ions and neutrons is briefly reviewed.In addition,the links to bridge the current advances on fundamental understandings to reactor applications are discussed to lay the groundwork between neutrons and ions for radiation effects studies. 展开更多
关键词 chemical disorder high-entropy alloys chemically complex alloys charged particles radiation resistance displacement damage electronic energy loss and ionization TRANSMUTATION
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Prototype of single-event effect localization system with CMOS pixel sensor 被引量:3
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作者 Jun Liu Zhuo Zhou +12 位作者 Dong Wang Shi-Qiang Zhou Xiang-Ming Sun Wei-Ping Ren Bi-Hui You Chao-Song Gao Le Xiao Ping Yang Di Guo Guang-Ming Huang Wei Zhou Cheng-Xin Zhao Min Wang 《Nuclear Science and Techniques》 SCIE EI CAS CSCD 2022年第11期10-20,共11页
The single-event effect(SEE) is a serious threat to electronics in radiation environments. The most important issue in radiation-hardening studies is the localization of the sensitive region in electronics to the SEE.... The single-event effect(SEE) is a serious threat to electronics in radiation environments. The most important issue in radiation-hardening studies is the localization of the sensitive region in electronics to the SEE. To solve this problem, a prototype based on a complementary metal oxide semiconductor(CMOS) pixel sensor, i.e., TopmetalM, was designed for SEE localization. A beam test was performed on the prototype at the radiation terminal of the Heavy Ion Research Facility in Lanzhou(HIRFL). The results indicated that the inherent deflection angle of the prototype to the beam was 1.7°, and the angular resolution was 0.6°. The prototype localized heavy ions with a position resolution of 3.4 μm. 展开更多
关键词 Single-event effect radiation resistant Topmetal-M
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Epoxy-POSS/silicone rubber nanocomposites with excellent thermal stability and radiation resistance 被引量:1
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作者 Mengni Shi Yinyong Ao +7 位作者 Lei Yu Lang Sheng Shuangxiao Li Jing Peng Hongbing Chen Wei Huang Jiuqiang Li Maolin Zhai 《Chinese Chemical Letters》 SCIE CAS CSCD 2022年第7期3534-3538,共5页
Due to the rigid Si-O-Si backbone,silicone rubber(SR)have a widespread application in extreme environment such as high temperature and high-level radiation.However,the radiation stability of SR still does not meet the... Due to the rigid Si-O-Si backbone,silicone rubber(SR)have a widespread application in extreme environment such as high temperature and high-level radiation.However,the radiation stability of SR still does not meet the practical needs in special radiation environments.Herein we prepared epoxy POSS(e POSS)/SR nanocomposites with excellent thermal stability and radiation resistance.As a physical crosslinking point in the SR,addition of small amount of ePOSS not only enhanced the mechanical properties of the matrix,but also improved its thermal stability greatly due to their good compatibility.e POSS/SR had higher radiation stability in air than SR owing to the inhibition of radiation oxidation by ePOSS,and the yield of main gaseous radiolysis products(CH_(4),H_(2),CO and CO_(2))of SR and ePOSS/SR nanocomposites was determined.By analyzing the changes of chemical structure,thermal properties and mechanical properties of the ePOSS/SR nanocomposite,combined with the characteristics of gas products afterγ-irradiation,the radiation induced crosslinking and degradation mechanism of the nanocomposites was proposed comprehensively. 展开更多
关键词 POSS Silicone rubber Thermal stability radiation resistance radiation crosslinking and degradation mechanism
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Effect of Temperature and Gamma-Ray Irradiation on Optical Characteristics of Fiber Bragg Grating Inscribed Radiation-Resistant Optical Fiber 被引量:3
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作者 Seongmin JU Youngwoong KIM +2 位作者 Kadathala LINGANNA Yune Hyoun KIM Won-Taek HAN 《Photonic Sensors》 SCIE EI CSCD 2020年第1期16-33,共18页
A new radiation-hard germano-silicate glass optical fiber with a pure silica glass buffer and a boron-doped silica glass inner cladding was fabricated for temperature sensor application based on the fiber Bragg gratin... A new radiation-hard germano-silicate glass optical fiber with a pure silica glass buffer and a boron-doped silica glass inner cladding was fabricated for temperature sensor application based on the fiber Bragg grating(FBG)underg-ray irradiation environment.The temperature dependences of optical attenuation at 1550.5 nm and Bragg reflection wavelength shift from 18℃to 40℃before theγ-ray irradiation were about 4.57´10^(-4)dB/℃and 5.48 pm/℃,respectively.The radiation-induced optical attenuation at 1550.5 nm and the radiation-induced Bragg reflection wavelength shift under theγ-ray irradiation with the total dose of 22.85 kGy at 35℃were about 0.03 dB/m and 0.12 nm,respectively,with theγ-ray irradiation sensitivity of 5.25´10^(-3)pm/Gy.The temperature and theγ-ray irradiation dependence of optical attenuation at 1550.5 nm in the FBG written fiber with boron-doped silica glass inner cladding were about 6 times and 4 times lower than that in the FBG written fiber without boron-doped silica glass inner cladding under a temperature change from 18℃to 40℃and theγ-ray irradiation with the total dose of 22.85 kGy at 35℃,respectively.Furthermore,the effect of temperature increase on the Bragg reflection wavelength of the FBG written fiber with boron-doped silica inner cladding was much larger about 1000 times than that of theγ-ray irradiation.However,no influence on the reflection power of the Bragg wavelengths and the full width at half maximum(FWHM)bandwidth under temperature and theγ-ray irradiation change was found.Also,after theγ-ray irradiation with the dose of 22.85 kGy,no significant change in the refractive index was found but the residual stresses developed in the fiber were slightly relaxed or retained. 展开更多
关键词 Optical fiber radiation resistance temperature sensor fiber Bragg grating radiation-induced attenuation
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Flexible, high sensitive and radiation-resistant pressure-sensing hydrogel
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作者 Zhiwen Jiang Yusong Wang +4 位作者 Guoqing Xu Zhuoni Jiang Zhiqing Ge Mozhen Wang Xuewu Ge 《Chinese Chemical Letters》 SCIE CAS CSCD 2022年第2期1011-1016,共6页
Excellent radiation resistance is a prerequisite for pressure-sensitive hydrogels to be used in high-energy radiation environments. In this work, tannic acid-modified boron nitride nanosheet(BNNS-TA) is first prepared... Excellent radiation resistance is a prerequisite for pressure-sensitive hydrogels to be used in high-energy radiation environments. In this work, tannic acid-modified boron nitride nanosheet(BNNS-TA) is first prepared as the radiation-resistant additive by a facile one-step ball milling of hexagonal boron nitride and tannic acid. Then, polyacrylamide(PAAm)-based pressure-sensitive hydrogel doped with BNNS-TA and Fe^(3+)ions is fabricated. The ternary BNNS-TA/Fe^(3+)/PAAm hydrogel exhibits excellent compressive strength(at least four times the compressive strength of unfilled pure PAAm hydrogel), pressure-sensitive performance(gauge factor is up to 1.4), and performance recovery due to the combination of multiple intermolecular interactions, such as covalent crosslinking, hydrogen bonds, and ion coordination interactions.The BNNS-TA/Fe^(3+)/PAAm hydrogel can be made as a pressure sensor installed in the control circuit or attached on the human body to detect human activities accurately. More importantly, the compressive strength and the pressure-sensitive performance of the BNNS-TA/Fe^(3+)/PAAm hydrogel can be maintained after the hydrogel is irradiated by^(60)Co gamma-ray at an absorbed dose of 15 k Gy. As a comparison, the compressive strength of the unfilled PAAm hydrogel is only a quarter of that before irradiation. This work not only reveals a facile method to achieve the preparation of chemically modified BNNS as a promising radiation-resistant additive but also provides a novel strategy for the development of pressure-sensitive hydrogel devices in radiation environments. 展开更多
关键词 Pressure-sensitive hydrogel POLYACRYLAMIDE radiation resistance Boron nitride nanosheet Tannic acid Motion detection
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Recent progress of radiation response in nanostructured tungsten for nuclear application
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作者 Hang Xu Lan-Li He +3 位作者 Yong-Feng Pei Chang-Zhong Jiang Wen-Qing Li Xiang-Heng Xiao 《Tungsten》 2021年第1期20-37,共18页
Engineering materials for nuclear reactors exposed to high-dose irradiation breed various radiation damage,leading to performance degradation of materials,which seriously limits the application of materials in the fut... Engineering materials for nuclear reactors exposed to high-dose irradiation breed various radiation damage,leading to performance degradation of materials,which seriously limits the application of materials in the future advanced nuclear reactors.Tungsten-based materials applied in future nuclear reactors have to withstand not only the attack of high-energy neutron and plasma,but also the repeated impact of steady-state or even transient thermal load.Researches in the past decades have proved that tailored nanostructure have advantage in annihilating radiation defects.With the rapid development of nanostructured tungsten,probing radiation application of nanostructured tungsten is of great significance in promoting the development of novel radiation-resistant materials.Herein,the development status of three kinds of nanostructured tungsten namely nanocrystalline,nanofilm and nanoporous tungsten designed for radiation tolerance and the performance enhancement mechanism of diverse nanostructure in irradiation environment is reviewed.Finally,future perspectives and technical challenges are discussed,to inspire more creative designs of novel nanostructured tungsten for radiation tolerance. 展开更多
关键词 TUNGSTEN NANOSTRUCTURE radiation damage radiation resistance
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Discovery of the inhibitor of DNA binding 1 as a novel marker for radioresistance in pancreatic cancer using genome-wide RNA-seq
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作者 scar Zuniga Stephanie Byrum Adam R.Wolfe 《Cancer Drug Resistance》 2022年第4期926-938,共13页
Purpose/Objective(s): Discovery of genetic drivers of radioresistance is critical for developing novel therapeuticstrategies to combine with radiotherapy of radioresistant PDAC. In this study, we used genome-wide RNA-... Purpose/Objective(s): Discovery of genetic drivers of radioresistance is critical for developing novel therapeuticstrategies to combine with radiotherapy of radioresistant PDAC. In this study, we used genome-wide RNA-seq toidentify genes upregulated in generated radioresistant PDAC cell lines and discovered the Inhibitor of DNA Binding1 (ID1) gene as a potential regulator of radioresistance in PDAC.Materials/Methods: Radioresistant clones of the PDAC cell lines MIA PaCa-2 and PANC-1 were generated bydelivering daily ionizing irradiation (IR) (2 Gy/day) in vitro over two weeks (total 20 Gy) followed by standardclonogenic assays following one week from the end of IR. The generated RR and parental cell lines were submittedfor RNA-seq analysis to identify differentially expressed genes. The Limma R package was used to calculatedifferential expression among genes. Log2 fold change values were calculated for each sample compared to thecontrol. Genes with an absolute fold change > 1 were considered significant. RNA sequencing expression data fromthe Cancer Genome Atlas (TCGA) database was analyzed through the online databases GEPIA, cBioPortal, and theHuman Protein Atlas.Results: Following exposure to two weeks of 2 Gy daily IR in vitro, the two PDAC cell lines showed significantlygreater clonogenic cell survival than their parental cell lines, indicating enhanced RR in these cells. RNA-seqanalysis comparing parental and RR cell lines found upregulated seven genes (TNS4, ZDHHC8P1, APLNR, AQP3,SPP1, ID1, ID2) and seven genes downregulated (PTX3, ITGB2, EPS8L1, ALDH1L2, KCNT2, ARHGAP9, IFI16) in bothRR cell lines. Western blotting confirmed increased expression of the ID1 protein in the RR cell lines compared totheir parental cell lines. We found that ID1 mRNA was significantly higher in PDAC tumors compared to matchednormal and high ID1 expression correlated with significantly worse disease-free survival (DFS) in PDAC patients(HR = 2.2, log rank P = 0.009). ID1 mRNA expression was also strongly correlated in tumors with TP53 mutation, aknown driver of radioresistance.Conclusion: Our analysis indicates a novel role of ID1 in PDAC radioresistance. ID1 expression is higher in tumortissue compared to normal, and high expression correlates with both worse DFS and association with the TP53mutation, suggesting that targeting ID1 prior to IR is an attractive strategy for overcoming radioresistance in PDAC. 展开更多
关键词 Pancreatic cancer radiation resistance ID1 RNA-SEQ
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Latest developments in room-temperature semiconductor neutron detectors: Prospects and challenges 被引量:1
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作者 Linyue Liu Xiao Ouyang +2 位作者 Runlong Gao Pengying Wan Xiaoping Ouyang 《Science China(Physics,Mechanics & Astronomy)》 SCIE EI CAS CSCD 2023年第3期11-31,共21页
Semiconductor-based neutron-detectors are characterized by small size, high energy-resolution, good spatial resolution, and stable response(at the depletion voltage). Consequently, these neutron-detectors are importan... Semiconductor-based neutron-detectors are characterized by small size, high energy-resolution, good spatial resolution, and stable response(at the depletion voltage). Consequently, these neutron-detectors are important for the fields of nuclear proliferation prevention, oil exploration, monitoring neutron-scattering experiments, cancer treatments, and space radiation effect research. However, there are some well-known problems for conventional silicon-based neutron detectors: low neutron-detection efficiency and limited resistance to radiation. Therefore, critical improvements are needed to enable sufficiently effective and practical neutron detection. To address these problems, direct-conversion neutron detectors as well as wide bandgap semiconductor-based detectors have been developed and studied intensely during the past years. Significant progress with respect to detection efficiency, radiation resistance, and room temperature operation was achieved. This paper reviews the latest research highlights, remaining challenges, and emerging technologies of direct-conversion neutron detectors as well as wide-bandgap semiconductor neutron detectors. This compact review serves as a reference for researchers interested in the design and development of improved neutron detectors in the future. 展开更多
关键词 fusion reaction neutron convertor neutron detectors wide bandgap semiconductor detection efficiency radiation resistance
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Future for inertial-fusion energy in Europe:a roadmap
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作者 Dimitri Batani Arnaud Colaitis +11 位作者 Fabrizio Consoli Colin N.Danson Leonida Antonio Gizzi Javier Honrubia Thomas Kühl Sebastien Le Pape Jean-Luc Miquel Jose Manuel Perlado R.H.H.Scott Michael Tatarakis Vladimir Tikhonchuk Luca Volpe 《High Power Laser Science and Engineering》 SCIE CAS CSCD 2023年第6期162-192,共31页
The recent achievement of fusion ignition with laser-driven technologies at the National Ignition Facility sets a historic accomplishment in fusion energy research.This accomplishment paves the way for using laser ine... The recent achievement of fusion ignition with laser-driven technologies at the National Ignition Facility sets a historic accomplishment in fusion energy research.This accomplishment paves the way for using laser inertial fusion as a viable approach for future energy production.Europe has a unique opportunity to empower research in this field internationally,and the scientific community is eager to engage in this journey.We propose establishing a European programme on inertial-fusion energy with the mission to demonstrate laser-driven ignition in the direct-drive scheme and to develop pathway technologies for the commercial fusion reactor.The proposed roadmap is based on four complementary axes:(ⅰ)the physics of laser-plasma interaction and burning plasmas;(ⅱ)high-energy high repetition rate laser technology;(ⅲ)fusion reactor technology and materials;and(ⅳ)reinforcement of the laser fusion community by international education and training programmes.We foresee collaboration with universities,research centres and industry and establishing joint activities with the private sector involved in laser fusion.This project aims to stimulate a broad range of high-profile industrial developments in laser,plasma and radiation technologies along with the expected high-level socio-economic impact. 展开更多
关键词 education and training fusion reactor technology high-energy laser high repetition rate laser inertial confinement fusion laser-plasma interaction public-private partnership radiation resistant materials
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Functional characterization of SAG/RBX2/ROC2/RNF7, an antioxidant protein and an E3 ubiquitin ligase 被引量:5
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作者 Yi Sun Hua Li 《Protein & Cell》 SCIE CSCD 2013年第2期103-116,共14页
SAG(Sensitive to Apoptosis Gene),also known as RBX2(RING box protein 2),ROC2(Regulator of Cullins 2),or RNF7(RING Finger Protein 7),was originally cloned in our laboratory as a redox inducible antioxi-dant protein and... SAG(Sensitive to Apoptosis Gene),also known as RBX2(RING box protein 2),ROC2(Regulator of Cullins 2),or RNF7(RING Finger Protein 7),was originally cloned in our laboratory as a redox inducible antioxi-dant protein and later characterized as the second member of the RBX/ROC RING component of the SCF(SKP1-CUL-F-box Proteins)E3 ubiquitin ligase.When acting alone,SAG scavenges oxygen radicals by forming inter-and intra-molecular disulfide bonds,whereas by forming a complex with other components of the SCF E3 ligase,SAG promotes ubiquitination and degradation of a number of protein substrates,includ-ing c-JUN,DEPTOR,HIF-1α,IκBα,NF1,NOXA,p27,and procaspase-3,thus regulating various signaling path-ways and biological processes.Specifically,SAG pro-tects cells from apoptosis,confers radioresistance,and plays an essential and non-redundant role in mouse embryogenesis and vasculogenesis.Furthermore,stress-inducible SAG is overexpressed in a number of human cancers and SAG overexpression correlates with poor patient prognosis.Finally,SAG transgenic expression in epidermis causes an early stage inhibi-tion,but later stage promotion,of skin tumorigenesis triggered by DMBA/TPA.Given its major role in pro-moting targeted degradation of tumor suppressive proteins,leading to apoptosis suppression and accel-erated tumorigenesis,SAG E3 ligase appears to be an attractive anticancer target. 展开更多
关键词 antioxidant angiogenesis apoptosis Cullin-RING ligases radiation resistance reactive oxygen species SAG/RBX2/ROC2/RNF7 SCF E3 ligases tumori-genesis ubiquitin ligase VASCULOGENESIS
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