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14-3-3蛋白研究进展 总被引:8,自引:1,他引:7
14-3-3蛋白是高度保守的、所有真核生物细胞中都普遍存在的、在大多数生物物种中由一个基因家族编码的一类蛋白调控家族。它几乎参与生命体所有的生理反应过程,人们在各种组织细胞中发现了各种不同的14-3-3蛋白。作为与磷酸丝氨酸/苏氨酸结合的第一信号分子,14-3-3蛋白在细胞的信号转导中起着至关重要的作用,尤其是它直接参与调节蛋白激酶和蛋白磷酸化酶的活性,被称为蛋白质与蛋白质相互作用的”桥梁蛋白”;它可以与转录因子结合形成复合体,调节相关基因的表达。一些研究表明,14-3-3蛋白调控机制的紊乱可以直接导致疾病的发生,在临床上14-3-3蛋白常常可以作为诊断的标志物。 相似文献
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Brock TG 《Neurochemical research》2008,33(5):801-807
Polyunsaturated fatty acids, like arachidonic acid, can bind proteins and affect their function. The 14-3-3 proteins bind
phosphorylated sites on a diverse array of client proteins and, in this way, are involved in many intracellular signaling
pathways. In this study, we used a novel approach to discover that 14-3-3ζ is able to directly bind arachidonic acid. Furthermore,
arachidonic acid, at physiological concentrations, reduced the binding of 14-3-3ζ to phosphorylated BAD, an interaction that
is important in regulating apoptosis. In addition, high concentrations of arachidonic acid caused the polymerization of 14-3-3ζ,
an event observed in neurodegenerative disorders. Taken together, these results indicate that arachidonic acid directly interacts
with 14-3-3ζ and that this interaction may be important in both normal and pathological cellular events. If so, then factors
that mediate the release, metabolism and reacylation of arachidonic acid into membranes represent key points of regulation. 相似文献
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14-3-3蛋白以二聚体形式存在,识别磷酸丝氨酸/苏氨酸连接的信号分子,通过与其配体蛋白质相互作用,参与细胞信号转导、细胞周期调控和细胞问运输。14-3-3蛋自在脑组织中含量丰富,所有神经元、星形胶质细胞、少突肢质细胞、小胶质细胞的胞液与胞核中都有表述。14-3-3蛋白与神经退行性疾病阿尔茨海默病和帕金森病的发生过程关系密切。 相似文献
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14-3-3蛋白与植物细胞信号转导 总被引:2,自引:0,他引:2
14-3-3蛋白通过直接蛋白质-蛋白质相互作用对植物代谢关键酶、质膜H^+ -ATP酶等发挥广泛调节作用。越来越多证据显示14-3-3蛋白通过与转录因子和其他信号分子结合参与调控植物细胞信号转导。对植物细胞中14-3-3蛋白调控信号转导途径,尤其是植物细胞对胁迫响应的调控机制进行了综述。 相似文献
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Aisha Qasim Butt Suaad Ahmed Ashwini Maratha Sinéad M. Miggin 《The Journal of biological chemistry》2012,287(46):38665-38679
Toll-like receptors (TLRs) are a group of pattern recognition receptors that play a crucial role in the induction of the innate immune response against bacterial and viral infections. TLR3 has emerged as a key sensor of viral double-stranded RNA. Thus, a clearer understanding of the biological processes that modulate TLR3 signaling is essential. Limited studies have applied proteomics toward understanding the dynamics of TLR signaling. Herein, a proteomics approach identified 14-3-3ϵ and 14-3-3σ proteins as new members of the TLR signaling complex. Toward the functional characterization of 14-3-3ϵ and 14-3-3σ in TLR signaling, we have shown that both of these proteins impair TLR2, TLR3, TLR4, TLR7/8, and TLR9 ligand-induced IL-6, TNFα, and IFN-β production. We also show that 14-3-3ϵ and 14-3-3σ impair TLR2-, TLR3-, TLR4-, TLR7/8-, and TLR9-mediated NF-κB and IFN-β reporter gene activity. Interestingly, although the 14-3-3 proteins inhibit poly(I:C)-mediated RANTES production, 14-3-3 proteins augment Pam3CSK4, LPS, R848, and CpG-mediated production of RANTES (regulated on activation normal T cell expressed and secreted) in a Mal (MyD88 adaptor-like)/MyD88-dependent manner. 14-3-3ϵ and 14-3-3σ also bind to the TLR adaptors and to both TRAF3 and TRAF6. Our study conclusively shows that 14-3-3ϵ and 14-3-3σ play a major regulatory role in balancing the host inflammatory response to viral and bacterial infections through modulation of the TLR signaling pathway. Thus, manipulation of 14-3-3 proteins may represent novel therapeutic targets for inflammatory conditions and infections. 相似文献
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14-3-3蛋白家族是一组高度保守的可溶性酸性蛋白质,分子量在28~33kD之间,广泛分布于各种真核生物之中。该蛋白能够特异地结合含有磷酸化丝氨酸或苏氨酸的肽段,参与多种信号转导途径。14-3-3蛋白调节着许多重要细胞生命活动,如:新陈代谢、细胞周期、细胞生长发育、细胞的存活和凋亡以及基因转录,该蛋白家族异常与疾病的发生密切相关,尤其是14-3-3蛋白在脑脊液中的分布与一些神经系统疾病密切相关。14-3-3蛋白已成为一些疾病的临床诊断指标,其作为疾病治疗的靶点也在研究之中。主要阐述了14-3-3蛋白的结构、功能、及其在疾病治疗中的应用。 相似文献
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Seven isoforms of 14-3-3 protein family have different functions in the cancer genesis and progress. It is found that six isoforms were up-regulated expression and inclined to sustain the cancer survival. Conversely, 14-3-3σ strongly promotes cancer apoptosis. Its down-regulated expression was found in many cancer tissues and thought to be an early event in the tumor genesis. Interestingly, no suggestions are made about the possible effect that the down-regulated expression of 14-3-3σ activated the other six 14-3-3 isoforms and they take over the role of 14-3-3σ in the tumor genesis. The inactivation of 14-3-3σ in the early stage of tumor genesis is a clue to trigger the other six 14-3-3 isoforms activation. 相似文献
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水稻14-3-3蛋白家族的生物信息学分析 总被引:12,自引:0,他引:12
通过隐马尔柯夫模型(Hidden Markov Model,HMM),对粳稻(Oryza sativa L.ssp.japonica)基因组的蛋白质数据库进行搜索,结果获得8个14—3—3蛋白的同源序列,其中发现4个新基因。通过对所有粳稻的14—3—3蛋白的DNA序列与各种表达序列标签(Expression Sequence Tags,ESTs)进一步比对,为14-3-3蛋白找到了ESTs的证据。结果说明这些基因在水稻不同的处理和不同的部位都有所表达,而且不同成员之间的表达模式存在较大的差异。蛋白质多序列联配分析结果表明,存在可能的功能多态位点。通过基因结构和染色体定位的分析,确认了水稻基因组中存在E样和非E样两类14-3-3蛋白。此外,对目前植物中的14—3—3家族作了初步的进化分析。 相似文献
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14-3-3蛋白家族是一组高度保守的可溶性酸性蛋白质,分子量在28~33kD之间,广泛分布于各种真核生物之中。该蛋白能够特异地结合含有磷酸化丝氨酸或苏氨酸的肽段,参与多种信号转导途径。14-3-3蛋白调节着许多重要细胞生命活动,如:新陈代谢、细胞周期、细胞生长发育、细胞的存活和凋亡以及基因转录,该蛋白家族异常与疾病的发生密切相关,尤其是14-3-3蛋白在脑脊液中的分布与一些神经系统疾病密切相关。14-3-3蛋白已成为一些疾病的临床诊断指标,其作为疾病治疗的靶点也在研究之中。主要阐述了14-3-3蛋白的结构、功能、及其在疾病治疗中的应用。 相似文献
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Pozuelo-Rubio M 《Autophagy》2011,7(2):240-242
Autophagy is an evolutionarily conserved pathway involved in a great variety of physiological roles such as starvation adaptation, elimination of microorganisms, and intracellular protein and organelle clearance. It seems clear that autophagy is strictly controlled because of the multiplicity of its functions and thus, autophagy components are finely regulated. Here, 14-3-3ζ protein has been shown as negative regulator of autophagy by association and inactivation of the vesicle nucleation component vacuolar protein sorting 34 (hVps34), the class III phosphatidylinositol-3- kinase (PI3KC3). 相似文献
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高等植物的3-羟基-3-甲基戊二酰辅酶A还原酶 总被引:3,自引:0,他引:3
介绍了植物3-羟基-3-甲基戊二酰辅酶A还原酶(HMGR)的结构和调控,并简略讨论了HMGR调控与植物类异戊二烯途径的关系. 相似文献