O-GlcNAc修饰对蛋白质泛素化降解途径的影响

O-GlcNAc修饰是一种特殊的糖基化修饰,几乎参与生物体内所有细胞过程的调控。该修饰与泛素化作为两种重要的蛋白质翻译后修饰形式,都与2型糖尿病、神经退行性疾病、癌症等疾病密切相关。O-GlcNAc修饰对蛋白质泛素化降解途径的影响主要体现在4个方面:(1)O-GlcNAc修饰能够抑制26S蛋白酶体的ATPase活性;(2)O-GlcNAc修饰会减少某些底物蛋白的泛素化降解;(3)O-GlcNAc修饰泛素化相关酶并调节其功能;(4)某些蛋白质(包括调控因子)发生O-GlcNAc修饰后间接影响蛋白质泛素化。     

O-GlcNAc修饰调控软骨及成骨分化的研究进展

O-GlcNAc糖基化属于蛋白质的翻译后修饰,参与了基因转录、信号转导、细胞分化等重要的细胞生命活动。软骨细胞与成骨细胞是骨骼系统中两种重要的细胞,它们的分化对骨的形成有重要意义。近年来研究表明O-GlcNAc糖基化通过调节多个信号通路中关键分子的活性影响软骨及成骨细胞的分化。为了更好的阐明O-GlcNAc糖基化调控软骨及成骨分化的分子机制,以期为骨关节炎、骨质疏松治疗提供新的干预靶点,我们对O-GlcNAc糖基化调控软骨及成骨分化的研究现状做如下综述。     

O-GlcNAc修饰蛋白质的生理功能和研究方法

氧连N-乙酰葡糖胺（O-GlcNAc）修饰是与磷酸化相类似的蛋白质翻译后修饰方式,它主要发生在细胞核和细胞质中的蛋白质上．与细胞信号通路密切相关,成为近年来的研究热点。该文主要从O-GlcNAc修饰蛋白质的生理功能和研究方法两方面介绍该领域近年来的研究成果。     

蛋白质O-GlcNAc糖基化的探针

生物大分子包括蛋白质、核酸、糖脂等的动态化学修饰与病理变化的关系,是当今生物医学研究最为重要的前沿领域之一。细胞内蛋白质丝氨酸和苏氨酸侧链羟基的O连N-乙酰葡糖胺(O-GlcNAc)糖基化修饰,参与了基因表达、信号转导、细胞周期等关键生物学过程的精密调控。异常的O-GlcNAc糖基化与肿瘤、糖尿病、神经退行性疾病等慢性疾病的发生发展密切相关。随着质谱检测技术和蛋白质组学的快速发展,目前已经有大量O-GlcNAc糖基化修饰靶蛋白质和位点得到鉴定。而其中多数蛋白质O-GlcNAc糖基化修饰的生理功能亟需通过探针进一步研究。本文对基于抗体、凝集素、代谢途径、化学酶法的O-GlcNAc糖基化探针研究进行归纳总结,发现未来对O-GlcNAc糖基化的研究急需开发针对特定位点的动态化研究探针,其对进一步揭示O-GlcNAc在疾病发生发展过程中的作用至关重要,也是实现临床分子诊断并进行靶向干预的关键。     

蛋白质O-GlcNAc糖基化及其细胞生物学功能

糖基化是蛋白质翻译后修饰的一项重要内容,大多数蛋白质糖基化发生在细胞膜表面,且糖链结构复杂。而发生在细胞浆与细胞核内的、单个O-GlcNAc修饰的蛋白质糖基化现象,因其独特的细胞定位、糖链连接方式以及重要的生物学调控作用而日益成为糖生物学领域研究的热点。现对蛋白质O-GlcNAc修饰及其细胞生物学功能研究进展情况进行综述。     

植物蛋白O-GlcNAc糖基化及生物学功能

蛋白质的O-GlcNAc糖基化现象发现迄今已有30多年历史.动物中,O-GlcNAc糖基化在调控细胞信号转导、基因转录、表观遗传和新陈代谢等方面发挥重要作用.而植物中,O-GlcNAc糖基化在近几年才得到关注并进行初步研究.本文对植物中O-GlcNAc修饰的糖供体合成途径、O-GlcNAc修饰关键酶、O-GlcNAc修饰蛋白的检测及功能等方面的研究工作进行归纳总结,发现O-GlcNAc糖基化在植物的生长发育、激素网络调控、信号转导、植物病毒侵染等过程均发挥重要作用,为进一步研究植物中O-GlcNAc糖基化的生物学功能提供参考.     

综述: 植物蛋白O-GlcNAc糖基化及生物学功能

蛋白质的O-GlcNAc糖基化现象发现迄今已有30多年历史．动物中,O-GlcNAc糖基化在调控细胞信号转导、基因转录、表观遗传和新陈代谢等方面发挥重要作用．而植物中,O-GlcNAc糖基化在近几年才得到关注并进行初步研究．本文对植物中O-GlcNAc修饰的糖供体合成途径、O-GlcNAc修饰关键酶、O-GlcNAc修饰蛋白的检测及功能等方面的研究工作进行归纳总结,发现O-GlcNAc糖基化在植物的生长发育、激素网络调控、信号转导、植物病毒侵染等过程均发挥重要作用,为进一步研究植物中O-GlcNAc糖基化的生物学功能提供参考．     

蛋白质O-GlcNAc修饰的检测技术

O-连接的N-乙酰葡糖胺（O-GlcNAc）修饰是位于细胞浆和细胞核蛋白质的丝氨酸或苏氨酸上的一种翻译后修饰,在高等真核生物细胞中广泛存在.越来越多的研究表明,O-GlcNAc修饰在代谢调控、压力应激、细胞周期、凋亡、糖尿病、心血管疾病和癌症等多种生理和病理过程中发挥重要作用,因此, O-GlcNAc修饰已受到众多生命科学领域研究人员的关注.然而,由于O-GlcNAc修饰与传统的N聚糖和O聚糖修饰有所不同,常规糖基化修饰的检测方法并不适用于O-GlcNAc.本文对O-GlcNAc修饰的检测及其修饰位点的确定方法进行了综述,并分析了各种方法的优缺点.     

泛素化修饰对疾病信号通路的调控

蛋白质在生物体的生理调控过程中发挥着重要的功能。在体内,蛋白质的合成、降解、活性与功能受到多种翻译后修饰的调控,其中泛素化修饰尤为重要。发现和阐明一些关键蛋白质的泛素化调控机制对理解蛋白质功能、细胞信号调控、疾病发病机理等都有着重要的作用。在这篇综述中,我们围绕与疾病相关的m TORC1和Hippo等关键信号通路,综述泛素化修饰在疾病相关信号通路中的重要作用。理解和阐明这些信号通路中关键蛋白的翻译后修饰调控机制将会进一步拓展我们对于细胞信号网络的认知。     

SUMO与乳腺癌

小泛素修饰物（Small ubiquitin-like modifier,SUMO）是结构上与泛素类似的一种修饰蛋白,能与一些特定的靶蛋白共价连接。与泛素介导蛋白质的降解不同,SUMO化修饰调控主要对靶蛋白的功能,如在蛋白质的稳定性、细胞定位、信号转导、基因转录调控等方面均发挥着重要的作用。最近的研究表明：SUMO与乳腺癌的发生发展密切相关,它是通过SUMO化修饰参与并影响雌激素受体信号通路来实现的,本文将就此做一综述。     

Molecular mechanisms regulating O-linked N-acetylglucosamine (O-GlcNAc)–processing enzymes

The post-translational modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc) dynamically programmes cellular physiology to maintain homoeostasis and tailor biochemical pathways to meet context-dependent cellular needs. Despite diverse roles of played by O-GlcNAc, only two enzymes act antagonistically to govern its cycling; O-GlcNAc transferase installs the monosaccharide on target proteins, and O-GlcNAc hydrolase removes it. The recent literature has exposed a network of mechanisms regulating these two enzymes to choreograph global, and target-specific, O-GlcNAc cycling in response to cellular stress and nutrient availability. Herein, we amalgamate these emerging mechanisms from a structural and molecular perspective to explore how the cell exerts fine control to regulate O-GlcNAcylation of diverse proteins in a selective fashion.     

The O-GlcNAcylation and its promotion to hepatocellular carcinoma

O-GlcNAcylation is a posttranslational modification that attaches O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins. Such a glycosylation would alter the activities, stabilities, and interactions of target proteins that are functional in a wide range of biological processes and diseases. Accumulating evidence indicates that O-GlcNAcylation is tightly associated with hepatocellular carcinoma (HCC) in its onset, growth, invasion and metastasis, drug resistance, and stemness. Here we summarize the discoveries of the role of O-GlcNAcylation in HCC and its function mechanism, aiming to deepen our understanding of HCC pathology, generate more biomarkers for its diagnosis and prognosis, and offer novel molecular targets for its treatment.     

O-GlcNAc modification of radial glial vimentin filaments in the developing chick brain

We examined the post-translational modification of intracellular proteins by β-O-linked N-acetylglucosamine (O-GlcNAc) with regard to neurofilament phosphorylation in the developing chick optic tectum. A regulated developmental pattern of O-GlcNAcylation was discovered in the developing brain. Most notably, discernible staining occurs along radial glial filaments but not along neuronal filaments in vivo. Immunohistochemical analyses in sections of progressive stages of development suggest upregulation of O-GlcNAc in the ependyma, tectofugal neuron bodies, and radial glial processes, but not in axons. In contrast, double-label immunostaining of monolayer cultures made from dissociated embryonic day (E) 7 optic tecta revealed O-GlcNAcylation of most axons. Labeling of brain sections together with Western blot analyses showed O-GlcNAc modification of a few discrete proteins throughout development, and suggested vimentin as the protein in radial glia. Immunoprecipitation of vimentin from E9 whole brain lysates confirmed O-GlcNAcylation of vimentin in development. These results indicate a regulated pattern of O-GlcNAc modification of vimentin filaments, which in turn suggests a role for O-GlcNAc-modified intermediate filaments in radial glia, but not in neurons during brain development. The control mechanisms that regulate this pattern in vivo, however, are disrupted when cells are placed in vitro.     

New ELISA-based method for the detection of O-GlcNAc transferase activity in vitro

O-GlcNAcylation is a dynamic, reversible, post-translational modification that regulates many cellular processes. O-GlcNAc transferase (OGT) is the sole enzyme transferring N-acetylglucosamine from uridine diphosphate (UDP)-GlcNAc to selected serine/threonine residues of cytoplasm and nucleus proteins. Aberrant of OGT activity is associated with several diseases, suggesting OGT as a novel therapeutic target. In this study, we created a new enzyme linked immunosorbent assays (ELISA)-based method for detection of OGT activity. First, casein kinase II (CKII), a well-known OGT substrate, was coated onto ELISA plate. Second, the GlcNAc transferred by OGT from UDP-GlcNAc to CKII was detected using an antibody to O-GlcNAc and then the horseradish peroxidase (HRP)-labeled secondary antibody. At last, 3,3′,5,5′-tetramethylbenzidine (TMB), the substrate of HRP, was used to detect the O-GlcNAcylation level of CKII which reflected the activity of OGT. Based on a series of optimization experiments, the RL2 antibody was selected for O-GlcNAc detection and the concentrations of CKII, OGT, and UDP-GlcNAc were determined in this study. ST045849, a commercial OGT inhibitor, was used to verify the functionality of the system. Altogether, this study showed a method that could be applied to detect OGT activity and screen OGT inhibitors.     

dbOGAP - An Integrated Bioinformatics Resource for Protein O-GlcNAcylation

Background  

Protein O-GlcNAcylation (or O-GlcNAc-ylation) is an O-linked glycosylation involving the transfer of β-N-acetylglucosamine to the hydroxyl group of serine or threonine residues of proteins. Growing evidences suggest that protein O-GlcNAcylation is common and is analogous to phosphorylation in modulating broad ranges of biological processes. However, compared to phosphorylation, the amount of protein O-GlcNAcylation data is relatively limited and its annotation in databases is scarce. Furthermore, a bioinformatics resource for O-GlcNAcylation is lacking, and an O-GlcNAcylation site prediction tool is much needed.