Roles of Axin in the Wnt Signaling Pathway

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.The Wnt signaling pathway plays important roles in cell shape, cell movement, cell adhesion, cell proliferation and differentiation, oncogenesis and development. Axin is an axis inhibitor. As a scaffold protein, it plays a critical role in the Wnt signaling pathway. Axin regulates the phosphorylation and stability of β-catenin via different mechanisms. It facilitates β-catenin degradation by assembling a β-catenin destruction complex including APC,GSK-3β,β-catenin,CKIα and axin itself. The homodimerization,nuclear-cytoplasmic shuttling,phosphorylation and stability of axin itself also play important roles in β-catenin regulation. In the Wnt signaling pathway, axin participates in the regulations of a series of biological effects such as axis development,cell death,neuronal differentiation and so on. As a newly recognized tumor suppressor,axin will provide a newly impactful means for diagnosis and therapy of cancer.福建省重大科技项目(No.2002F002)资助~

Cloning and characterization of G protein beta 1 subunit in shrimp Litopenaeus vannamei

根据G蛋白Gβ1亚基的保守序列设计简并引物,通过简并PCR和RACE技术,克隆到凡纳滨对虾(Litopenaeusvannamei)Gβ1基因的全长cDNA序列。利用Blast、DNAstar和Genedoc软件分析,发现该Gβ1编码的蛋白序列与其他物种已知的Gβ1序列具有相当高的保守性,将它命名为pvGβ1。免疫共沉淀分析发现pvGβ1能在体外适当条件下与对虾Gαs或Gαq相互结合。Westernblot-ting分析发现,pvGβ1在对虾身体各部位都有广泛分布,尤其在脑神经、眼和眼柄有大量表达。说明了Gβ1在对虾的神经系统和光信号传导等生命过程中的重要性。 【英文摘要】 The β/γ-subunits of the heterotrimeric GTP-binding proteins are important regulators of G-protein alpha subunits as well as a series of signal transduction receptors and effectors. In this study, a novel G protein β_1 subunit was isolated from shrimp Litopenaeus vannamei, and was termed pvGβ_1. Sequence analysis showed that the pvGβ_1 protein contained all the well-conserved domains and motifs that were critical sites for interaction with receptors and other binding effectors. Co-immunoprecipitation assay d...国家863计划项目(2002AA629060)资

An Investigation of the Professional Development of Primary and Secondary School P. E. Backbone Teachers in Fujian Province

采用文献法、调查法、统计法、逻辑法等研究方法,以参加2013—2015年福建省基础教育万名骨干教师培训中的190名中小学体育骨干教师为调查对象,对教师基本情况和教师专业发展的认识、态度、知识、能力、继续教育等现状进行调查,在此基础上对教师专业发展现状进行分析,总结出我省中小学体育骨干教师专业发展的特点及存在的问题,并提出相应的建议,给我省中小学体育教师培训机构的改革提供依据,同时为我省中小学体育教师专业发展提供参考与借鉴,为进一步深化我省中小学体育教育改革提供人才保障.结果表明:1)目前,福建省中小学体育骨干教师以年富力强者居多,年龄、职称结构较合理;教师专业发展意识强,学历层次由大专逐步向本科、硕士过度,但硕士比例小;2)教师专业发展态度端正,职业的稳定性和责任感强烈,但部分年轻教师缺乏专业发展的自主性;3)教师对专业知识的掌握比较扎实,主要通过互联网、图书资料、专家报告或讲座等方法来获取专业知识;4)专业能力水平方面,教师在体育教学、课外指导、体育保健、现代教育技术运用等方面能力比较强,而创新教育和科研两方面能力相对比较薄弱;5)当下,我省中小学体育骨干教师最需要强化的培训是课题申报技能、论文写作能力、专题讲座能力、教育科研方法、提高学历层次、教学设计能力,其中提高科研能力和水平是教师们最迫切的愿望.2014年福建省中青年教师教育科研项目(社科A类)(JAS14023

Mapping QTLs for Rice Grain Shape with QTL×Environment Interactions and Epistatic Effects Analysis

利用广陆矮4号x佳辐占水稻重组自交系构建了SSr标记的遗传图谱.联合2007年和2008年获得的两组稻米粒长(gl)、粒宽(gW)、长宽比(l/W)数据应用混合线性模型方法进行QTl定位,并作加性效应、加性x加性上位互作效应以及加性QTl、上位性QTl与环境的互作效应分析.结果显示;(1)在加性效应分析中两个群体共检测到4个控制粒长的QTl,4个控制粒宽的QTl,5个控制长宽比的QTl,贡献率分别为13.81%、15.36%和16.29%.(2)在上位互作效应分析中两个群体共检测到2对控制粒长的互作QTl,1对控制粒宽的互作QTl,3对控制长宽比的互作QTl,贡献率分别为5.77%、2.59%和7.42%.(3)环境互作检测中,发现共有13个加性QTl和4对QTl的加性x加性上位性与环境产生了互作效应.结果表明,上位性效应和加性效应都影响稻米粒形遗传,QE互作效应也对粒形有着显著的影响.In this study,a recombinant inbred line (RIL) population derived from the indica-indica rice cross ‘Guangluai 4’בJiafuzhan’ was used in mapping of Quantitative trait loci (QTLs).Based on mixed linear model QTLmapper1.6,mapping was carried out for grain shape such as grain length (GL),grain width (GW) and length-width ratio (L/W) in rice in 2007 and 2008.QTLs were determined at the one-locus and two-locus levels,and QTL-by-environment (QE) interactions were analyzed.Four,four and five QTLs were detected to have significant additive effects for GL,GW and L/W,and the contribution rate were 13.81%,15.36% and 16.29%,respectively.Two,one and three pairs of epistatic QTLs with significant additive-by-additive (AA) interaction effects (epistatic effects) were identified for the three traits,and the contribution rate were 5.77%,2.59% and 7.42%,respectively.Significant QE interactions were found for thirteen QTLs with additive effects and four pairs of epistatic QTLs.The results indicated that the epistatic and additive effects played an important role on the inheritance of grain shape,and the environmental factor had significant effects on the three traits.国家863计划项目(2007AA10Z179);福建省科技计划重点项目(2008N0122);厦门大学科技创新项目(XDKJCX20063004

Determinants that control the specific interactions between TAB1 and p38α

Previous studies have revealed that transforming growth factor-beta-activated protein kinase 1 (TAB1) interacts with p38 alpha and induces p38 alpha autophosphorylation. Here, we examine the sequence requirements in TAB1 and p38 alpha that drive their interaction. Deletion and point mutations in TAB1 reveal that a proline residue in the C terminus of TAB1 (Pro412) is necessary for its interaction with p38 alpha. Furthermore, a cryptic D-domain-like docking site was identified adjacent to the N terminus of Pro412, putting Pro412 in the (phi(B)+3 position of the docking site. Through mutational analysis, we found that the previously identified hydrophobic docking groove in p38 alpha is involved in this interaction, whereas the CD domain and ED domain are not. Furthermore, chimeric analysis with p38 beta (which does not bind to TAB1) revealed a previously unidentified locus of p38 alpha comprising Thr218 and Ile275 that is essential for specific binding of p38 alpha to TAB1. Converting either of these residues to the corresponding amino acid of p380 abolishes p38 alpha interaction with TAB1. These p38a mutants still can be fully activated by p38 alpha upstream activating kinase mitogen-activated protein kinase kinase 6, but their basal activity and activation in response to some extracellular stimuli are reduced. Adjacent to Thr218 and Ile275 is a site where large conformational changes occur in the presence of docking-site peptides derived from p38 alpha substrates and activators. This suggests that TAB1-induced autophosphorylation of p38 alpha results from conformational changes that are similar but unique to those seen in p38 alpha interactions with its substrates and activating kinases

基于大学生化学实验大赛的无机化学实验教学设计

介绍了福建省第二届大学生化学实验大赛无机化学实验考试的基本情况,分析了存在的问题。并以大赛试题为案例,针对存在的问题,结合翻转课堂模式,详细设计新的教学方案,实现真正意义的教学互动,切实提高实验教学水平。福建省本科高校教育教学改革项目(FBJG20180097);;厦门大学教学改革研究项目(JG20180105,JG20180132

AMP as a Low-Energy Charge Signal Autonomously Initiates Assembly of AXIN-AMPK-LKB1 Complex for AMPK Activation

The AMP-activated protein kinase (AMPK) is a master regulator of metabolic homeostasis by sensing cellular energy status. AMPK is mainly activated via phosphorylation by LKB1 when cellular AMP/ADP levels are increased. However, how AMP/ADP brings about AMPK phosphorylation remains unclear. Here, we show that it is AMP, but not ADP, that drives AXIN to directly tether LKB1 to phosphorylate AMPK. The complex formation of AXIN-AMPK-LKB1 is greatly enhanced in glucose-starved or AICAR-treated cells and in cell-free systems supplemented with exogenous AMP. Depletion of AXIN abrogated starvation-induced AMPK-LKB1 colocalization. Importantly, adenovirus-based knockdown of AXIN in the mouse liver impaired AMPK activation and caused exacerbated fatty liver after starvation, underscoring an essential role of AXIN in AMPK activation. These findings demonstrate an initiating role of AMP and demonstrate that AXIN directly transmits AMP binding of AMPK to its activation by LKB1, uncovering the mechanistic route for AMP to elicit AMPK activation by LKB1.http://news.xmu.edu.cn/s/13/t/542/22/a9/info139945.ht

The Lysosomal v-ATPase-Ragulator Complex Is a Common Activator for AMPK and mTORC1, Acting as a Switch between Catabolism and Anabolism

林圣彩教授课题组长期致力于细胞信号转导的研究。近年来，该课题组潜心研究，不断攻关，取得了一系列重大成果，如揭示细胞如何应对生长因子缺乏的内在机理，发现了细胞自噬“路线图”、还发现了细胞如何感应“饥饿”信号AMP的信号传导通路等。其中，“发现细胞自噬‘路线图’”成果曾登上《科学》杂志，并入选2012年度“中国科学十大进展”。AMPK and mTOR play principal roles in governing metabolic programs; however, mechanisms underlying the coordination of the two inversely regulated kinases remain unclear. In this study we found, most surprisingly, that the late endosomal/lysosomal protein complex v-ATPase-Ragulator, essential for activation of mTORC1, is also required for AMPK activation. We also uncovered that AMPK is a residential protein of late endosome/lysosome. Under glucose starvation, the v-ATPase-Ragulator complex is accessible to AXIN/LKB1 for AMPK activation. Concurrently, the guanine nucleotide exchange factor (GEF) activity of Ragulator toward RAG is inhibited by AXIN, causing dissociation from endosome and inactivation of mTORC1. We have thus revealed that the v-ATPase-Ragulator complex is also an initiating sensor for energy stress and meanwhile serves as an endosomal docking site for LKB1-mediated AMPK activation by forming the v-ATPase-Ragulator-AXIN/LKB1-AMPK complex, thereby providing a switch between catabolism and anabolism. Our current study also emphasizes a general role of late endosome/lysosome in controlling metabolic programs

The Regulation Mechanism of MdmX in Axin-p53Signaling Pathway

鼠双微体基因X(MdMX)是肿瘤抑制因子P53信号通路中重要的负调控蛋白,它能与P53直接结合,抑制P53的转录活性.体轴发育抑制因子AXIn作为构架蛋白与P53及同源结构域互作蛋白激酶2(HIPk2)等相互作用形成复合物,诱导P53的转录活化,共同促进细胞的凋亡.本研究将MdMX引入AXIn-P53信号通路的调控中,发现MdMX通过竞争AXIn与P53的结合,抑制AXIn诱导P53的转录激活.P53结合区域缺失的MdMX突变体MdMXΔP53则不能抑制AXIn对P53的激活.这些实验结果为进一步深入研究AXIn-P53信号通路在细胞凋亡及肿瘤发生发展中的作用提供了重要的理论依据.Mouse double minute X(MdmX)is a key negative regulator of the tumor suppressor p53.It directly interacts with p53, and inhibits the transcriptional activity of p53.Axin(Axis inhibitor)is an essential scaffold protein participating in many signaling pathways including Wnt signaling,the JNK MAP kinase cascade,TGF-βsignaling as well as p53signaling.It forms a p53activating complex to induce the apoptosis-related p53transcriptional activation.To evaluate the function of MdmX in Axin-p53signaling pathway,p53-luciferase reporter gene assay and Co-immunoprecipitation experiments were conducted.Here,we show that MdmX can inhibit Axin-induced p53transcriptional activation by competing the interaction of p53with Axin.MdmXΔp53,a MdmX deletion mutant that lacks p53binding domain,fails to exert the inhibitory effect.These results provide the foundation for further study on the role of Axin-p53signaling pathway in cell apoptosis and tumorigenesis.国家自然科学基金(31101014

Mechanism of Tumorigenesis Regulated by Axin

阐明肿瘤发生机制的细胞信号转导途径的研究是当今生物医学领域研究的热点。Axin是一个肿瘤抑制因子,它以构架蛋白的形式在Wnt、JNK、p53、TGF-β、G蛋白信号转导途径等众多信号转导途径中参与细胞生长、增殖、分化、癌变和凋亡等多种重要细胞命运的调控过程。现从Axin的发现、Axin通过多种信号转导途径抑制肿瘤发生和AXIN1基因突变与肿瘤发生之间的关系这三个方面介绍肿瘤抑制因子Axin与肿瘤之间的研究进展。 【英文摘要】 Cell signaling pathways involved in tumorigenesis are the focus of biomedical research nowadays. Axin, a tumor suppressor, is an essential scaffold protein participating in a network of separate but interacting signaling transduction pathways. Emerging evidence indicates its diverse roles in Wnt, JNK, p53, TGF and G-protein signaling pathways to regulate cellular fate determination, growth and proliferation. In this light, there has been intense investigation into the pivotal nature of Axin in assuring appr..