E3泛素连接酶和小泛素蛋白样修饰蛋白在子痫前期发病机制中的研究进展

子痫前期(pre-eclampsia, PE)是一种常见的严重妊娠并发症,其病因和发病机制至今尚未完全阐明,目前的研究表明泛素化和类泛素化修饰在PE发生发展中起着重要作用。E3泛素连接酶作为泛素化修饰的关键酶之一,对PE的影响至关重要。而在与泛素化修饰密切相关的类泛素化修饰中,小泛素蛋白样修饰蛋白(small ubiquitin-related modifier proteins, SUMO)显著地影响了PE的进展。本综述将着重讨论E3泛素连接酶和小泛素蛋白样修饰蛋白在PE发病机制中的作用。     

SENP5 mediates breast cancer invasion via a TGFβRI SUMOylation cascade

Identifying novel mechanisms, which are at the core of breast cancer biology, is of critical importance. Such mechanisms may explain response to treatment, reveal novel targets or drive detection assays.To uncover such novel mechanisms, we used survival analysis on gene expression datasets encompassing 1363 patients. By iterating over the compendia of genes, we screened for their significance as prognosis biomarkers and identified SUMO-specific protease 5 (SENP5) to significantly stratify patients into two survival groups across five unrelated tested datasets. According to these findings, low expression of SENP5 is associated with good prognosis among breast cancer patients.Following these findings, we analyzed SENP5 silencing and show it is followed by inhibition of anchorage-independence growth, proliferation, migration and invasion in breast cancer cell lines. We further show that these changes are conducted via regulation of TGFβRI levels. These data relate to recent reports about the SUMOylation of TGFβRI. Following TGFβRI changes in expression, we show that one of its target genes, MMP9, which plays a key role in degrading the extracellular matrix and contributes to TGFβ-induced invasion, is dramatically down regulated upon SENP5 silencing.This is the first report represents SENP5-TGFβ-MMP9 cascade and its mechanistic involvement in breast cancer.     

PML翻译后修饰在肿瘤细胞中的研究进展

<正>早幼粒细胞白血病(promyelocytic leukemia,PML)基因最初被发现于急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)中,在大部分APL病例中发现染色体异位t(15;17),即17号染色体上的维甲酸受体α(retinoic acid receptorα,RARα)基因与位于15号染色体上的PML基因相互异位,产生新的融合蛋白PML-RARα,这种融合蛋白在APL中发挥重要的作用[1]。PML蛋白又称TRIM19,属于     

亨廷顿蛋白的翻译后修饰在亨廷顿病发病机制中的作用(英文)

翻译后修饰能快速、有效且可逆地调节蛋白的稳定性、分布位置、功能及其与其它分子之间的相互作用。翻译后修饰主要包括氨基酸残基的SUMO化、磷酸化、棕榈化以及乙酰化等。这些复杂的生化修饰能严格、规范地调节各种细胞过程。亨廷顿蛋白(Htt)的几种翻译后修饰方式已见报道。这些翻译后修饰会影响Htt的代谢、Htt与其它蛋白质的相互作用以及Htt的细胞毒性。突变Htt的剪切、清除以及与其它细胞蛋白质的相互作用是导致亨廷顿病的重要生化事件。因此,了解Htt修饰的信号转导及其意义,可以帮助我们更好地理解野生型Htt的正常功能和突变Htt的致病机制。     

Sumoylation of vimentin354 is associated with PIAS3 inhibition of glioma cell migration

The invasive phenotype of glioblastoma multiforme (GBM) is a hallmark of malignant process, yet the molecular mechanisms that dictate this locally invasive behavior remain poorly understood. Over-expression of PIAS3 effectively changes cell shape and inhibits GBM cell migration. We focused on the molecular target(s) of PIAS3 stimulated sumoylation, which play an important role in the inhibition of GBM cell motility. Here we report, through the immunoprecipitation with SUMO1 antibody, followed by proteomic analysis, the identification of vimentin (vimentin354), a nuclear component in GBM cells, as the main target of sumoylation promoted by PIAS3.     

Posttranslational Modifications of HIV-1 Integrase by Various Cellular Proteins during Viral Replication

HIV-1 integrase (IN) is a key viral enzyme during HIV-1 replication that catalyzes the insertion of viral DNA into the host genome. Recent studies have provided important insights into the multiple posttranslational modifications (PTMs) of IN (e.g., ubiquitination, SUMOylation, acetylation and phosphorylation), which regulate its multifaceted functions. A number of host cellular proteins, including Lens Epithelium‑derived Growth factor (LEDGF/p75), p300 and Ku70 have been shown to interact with IN and be involved in the PTM process of IN, either facilitating or counteracting the IN PTMs. Although previous studies have revealed much about the important roles of IN PTMs, how IN functions are fine-tuned by these PTMs under the physiological setting still needs to be determined. Here, we review the advances in the understanding of the mechanisms and roles of multiple IN PTMs.     

中医药靶向调节线粒体动力学及相关蛋白SUMO化修饰防治脑缺血/再灌注损伤的研究进展

线粒体稳态失衡在脑缺血/再灌注损伤（cerebral ischemia/reperfusion injury,CI/RI）病理过程中扮演重要角色。线粒体分裂/融合的动态调节（线粒体动力学）作为线粒体质量控制（mitochondrial quality control,MQC）的关键环节，在CI/RI中维持线粒体稳态发挥重要作用。小泛素相关修饰物（small ubiquitin-related modifier,SUMO）修饰是一类存在于细胞内动态可逆的蛋白质翻译后修饰形式，通过对底物蛋白进行多步酶促反应以完成对靶蛋白的SUMO修饰和去SUMO修饰过程，进而影响底物蛋白的亚细胞定位、蛋白互作和稳定性，其普遍参与了蛋白转运、信号传导、DNA修复、炎症反应及氧化应激等病理生理过程。线粒体动力学及相关蛋白通过SUMO化修饰调控线粒体融合和分裂，进而调节线粒体稳态，在CI/RI进展与转归中发挥着关键作用。中药在防治缺血性脑病方面具有明显优势，综述了线粒体分裂/融合过程中相关蛋白的SUMO化修饰的调节机制，以及靶向调节线粒体动力学及相关蛋白SUMO化修饰防治CI/RI的中医药研究进展，以期为缺血性...