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Wnt信号转导途径是调控细胞形状、运动、黏附、增殖、分化、癌变及机体发育等过程的主要途径之一.Axin(轴蛋白)是一个体轴发育抑制因子,作为构架蛋白在Wnt信号转导途径中起着关键的作用.Axin通过不同的机制调节β连环蛋白的磷酸化和稳定性.它通过与APC、GSK-3β、β连环蛋白和CKIα结合形成复合体促进β连环蛋白的降解,还通过同源二聚化、核质穿梭、自身磷酸化和稳定性的调控来调节β连环蛋白的稳定性.Axin通过Wnt信号转导途径参与了一系列生物学效应的调控,如体轴发育、细胞死亡、神经元的分化等.作为一个新发现的肿瘤抑制因子,axin将为癌症的诊断和治疗提供新的有效的手段. 相似文献
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R-Ras属于小分子G蛋白Ras超家族,在细胞信号转导通路中起着分子开关的作用,具有调控细胞黏附、促进细胞凋亡、抑制细胞运动、调节细胞形态等多种生物学功能。R-Ras和Ras家族的其他成员一样,结合GTP时处于激活状态,即信号通路开启状态,能够与下游因子相互作用;通过上游信号的调节及其下游效应物,将胞外信号转导到胞内,调节细胞的相关生物学功能。最近的研究提示R-Ras与乳腺癌等肿瘤的发生具有相关性,对其深入研究有可能为肿瘤发生机制的阐明提供分子基础。我们对R-Ras介导的细胞信号转导通路及其生物学功能进行简要综述。 相似文献
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泛素-蛋白酶体途径及其生物学作用的研究进展 总被引:3,自引:0,他引:3
泛素-蛋白酶体途径是细胞内重要的非溶酶体蛋白降解途径,是调节各种细胞生物学过程的重要机制,参与调节细胞周期进程、细胞增生与分化以及信号转导等各种细胞生理过程,对维持细胞正常生理功能具有十分重要的意义。本文简要介绍了泛素-蛋白酶体途径的作用过程,并从其对某些抑癌基因、转录因子和细胞周期素依赖性激酶抑制蛋白的调节,参与肿瘤及癌症的发生和发展,讨论其生物学作用,并指出其在药物研究方面的重要作用。 相似文献
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转化生长因子-β(transforming growth factor-β,TGF-β)是一种具有多种生物学活性的细胞因子,参与调节细胞的增殖、分化、凋亡和胚胎发育等多种生命活动。TGF-β在肿瘤发生、发展中具有双重作用:在肿瘤发生的起始阶段TGF-β抑制肿瘤生长,而在进展期TGF-β起着促进肿瘤浸润转移的作用。研究表明TGF-β/Smads信号通路中任何一个环节出现异常都可导致信号转导的紊乱,从而导致胃癌的发生与发展。 相似文献
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巨噬细胞游走抑制因子是一种具有多种生物学效应的糖蛋白,可以调节不同的下游信号如ERK/AKT、NF-κB等通路参与肿瘤细胞增殖、侵袭、转移、血管形成和自噬等生物学过程。临床相关研究表明巨噬细胞游走抑制因子与肿瘤发生发展关系密切,且在乳腺癌、肺癌、前列腺癌、甲状腺癌、结肠癌等多种肿瘤中高表达,因此以巨噬细胞游走抑制因子为靶点的相关肿瘤治疗逐渐受到重视。有关巨噬细胞游走抑制因子拓扑异构酶活性抑制剂及巨噬细胞游走抑制因子中和抗体在肿瘤治疗中的研究越来越多。本文对巨噬细胞游走抑制因子在肿瘤发生发展中的作用以及针对巨噬细胞游走抑制因子进行的肿瘤治疗研究作一综述。 相似文献
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Axin was originally identified from the characterization of the Fused locus, the disruption of which leads to duplication of axis and embryonic lethality. It is a multidomain protein that interacts with multiple proteins and functions as a negative regulator of Wnt signaling by downregulating the beta-catenin levels. Recently, it was demonstrated that Axin also plays an important role in a JNK signaling pathway. Axin utilizes discriminatory domains for its distinct roles in the Wnt pathway and in the Axin/JNK pathway. Here we review the data that show how Axin regulates multiple signaling pathways by serving as a scaffold protein, controlling diverse cellular functions in proliferation, fate determination, and suppression of tumorigenesis. 相似文献
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Cloning of the human homolog of conductin (AXIN2), a gene mapping to chromosome 17q23-q24 总被引:5,自引:0,他引:5
Conductin or Axil, an Axin homolog, plays an important role in the regulation of beta-catenin stability in the Wnt signaling pathway. To facilitate the molecular analysis of the human gene, we isolated the human homolog, AXIN2. The cDNA contains a 2529-bp open reading frame and encodes a putative protein of 843 amino acids. Compared with rat and mouse homologs, AXIN2 shows an overall 89% amino acid identity. Several functional domains in this protein are highly conserved including the GRS (95.9%), GSK-3beta (96.3%), Dsh (98%), and beta-catenin (89.9%) domains. Radiation hybrid mapping localized the AXIN2 gene to human chromosome 17q23-q24, a region that shows frequent loss of heterozygosity in breast cancer, neuroblastoma, and other tumors. Human AXIN2 is thus a very strong candidate involved in multiple tumor types. 相似文献
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沉默信息调节因子1(SIRT1)是Sirtuin 家族中的一员,属于烟酰胺(NAD+)依赖的Ⅲ类组蛋白去乙酰化酶,能通过对多种非组蛋白及组蛋白赖氨酸残基进行去乙酰化修饰调节基因表达。近来的研究发现,SIRT1不仅能使肿瘤抑制因子去乙酰化,促进肿瘤发生,还能使肿瘤促进因子去乙酰化,抑制肿瘤发生。SIRT1与肿瘤的生物学特性密切相关,影响肿瘤分期及患者预后。在消化系统肿瘤中,SIRT1具有双面性,既可作为抑癌因子,也可发挥癌因子的作用。近年来,许多研究对SIRT1在肿瘤中的作用靶点及相关信号通路做了深入研究,关于SIRT1在肿瘤中作用机制的新研究不断出现。SIRT1已成为人们攻克肿瘤的一个研究热点。本文通过对SIRT1在肿瘤中的双重作用,尤其是在消化系统肿瘤中的不同作用靶点和参与的信号通路作一综述,希望为临床上治疗消化系统肿瘤提供更有说服力的证据。 相似文献
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Callow MG Tran H Phu L Lau T Lee J Sandoval WN Liu PS Bheddah S Tao J Lill JR Hongo JA Davis D Kirkpatrick DS Polakis P Costa M 《PloS one》2011,6(7):e22595
Canonical Wnt signaling is controlled intracellularly by the level of β-catenin protein, which is dependent on Axin scaffolding of a complex that phosphorylates β-catenin to target it for ubiquitylation and proteasomal degradation. This function of Axin is counteracted through relocalization of Axin protein to the Wnt receptor complex to allow for ligand-activated Wnt signaling. AXIN1 and AXIN2 protein levels are regulated by tankyrase-mediated poly(ADP-ribosyl)ation (PARsylation), which destabilizes Axin and promotes signaling. Mechanistically, how tankyrase limits Axin protein accumulation, and how tankyrase levels and activity are regulated for this function, are currently under investigation. By RNAi screening, we identified the RNF146 RING-type ubiquitin E3 ligase as a positive regulator of Wnt signaling that operates with tankyrase to maintain low steady-state levels of Axin proteins. RNF146 also destabilizes tankyrases TNKS1 and TNKS2 proteins and, in a reciprocal relationship, tankyrase activity reduces RNF146 protein levels. We show that RNF146, tankyrase, and Axin form a protein complex, and that RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation. RNF146 is a cytoplasmic protein that also prevents tankyrase protein aggregation at a centrosomal location. Tankyrase auto-PARsylation and PARsylation of Axin is known to lead to proteasome-mediated degradation of these proteins, and we demonstrate that, through ubiquitylation, RNF146 mediates this process to regulate Wnt signaling. 相似文献