SUMO E3连接酶在植物生长发育中的功能研究进展

SUMO化是真核生物中一种重要的蛋白质翻译后修饰。SUMO E3连接酶具有对底物特异的识别功能, 可以促进SUMO化反应, 是SUMO化修饰过程中的重要组成部分。目前, 在植物中已经鉴定出多种SUMO E3连接酶, 它们参与植物重要器官的发育调控。该文对植物SUMO E3连接酶在根系发育、开花途径、配子发育和光形态建成中的作用及其调节机制进行综述。     

PIAS1对PRRSV N蛋白SUMO化修饰及病毒复制的影响

【目的】猪繁殖与呼吸综合征病毒(PRRSV)是一种危害全球养猪业的重要病原。SUMO(Small ubiquitin-like modifier)化修饰作为一种可逆的翻译后修饰在调节病毒复制方面发挥着重要功能。PIAS1(Protein inhibitor of activated STAT1)是SUMO E3连接酶PIAS家族的一员,可以促进靶蛋白的SUMO化修饰,进而影响靶蛋白的功能,参与基因转录调控过程。探究PIAS1与PRRSV N蛋白相互作用的机制及其对N蛋白SUMO化修饰和病毒复制的影响,为进一步阐明PRRSV复制调控和致病的分子机制提供科学依据。【方法】利用酵母回复杂交、免疫共沉淀和激光共聚焦技术验证N蛋白与PIAS1的相互作用;以递增剂量外源性转染PIAS1观察其是否介导N蛋白SUMO化修饰;采用RNA干扰和慢病毒转导技术测定PIAS1对PRRSV复制的影响。【结果】PIAS1能与N蛋白相互作用,而且两者主要共定位于胞浆中;外源转染PIAS1并未增加N蛋白SUMO化修饰水平;在MARC-145细胞中,PIAS1的表达有利于PRRSV的复制。【结论】PIAS1可促进PRRSV的复制。     

UBC9与癌症的研究进展CSCD

泛素样小分子修饰因子SUMO家族蛋白主要参与蛋白质翻译后功能的调节,在转录、DNA修复、核质物质转运及染色体分离等方面发挥重要的作用。SUMO修饰包括活化、结合、连接和解离,涉及多个酶多个步骤的催化过程。研究发现,UBC9是目前发现的SUMO修饰靶蛋白过程中唯一的E2结合酶,在SUMO修饰过程中发挥关键作用,是SUMO修饰过程中的关键节点。越来越多的研究表明,UBC9和肿瘤的发生、发展关系密切,UBC9在许多恶性肿瘤如乳腺癌、卵巢癌中都呈高表达状态,改变癌细胞中UBC9基因的表达可导致细胞增殖及细胞周期的变化,UBC9和癌症的关系成为现在主要的研究热点之一。     

UBC9与癌症的研究进展

泛素样小分子修饰因子SUMO家族蛋白主要参与蛋白质翻译后功能的调节,在转录、DNA修复、核质物质转运及染色体分离等方面发挥重要的作用。SUMO修饰包括活化、结合、连接和解离,涉及多个酶多个步骤的催化过程。研究发现,UBC9是目前发现的SUMO修饰靶蛋白过程中唯一的E2结合酶,在SUMO修饰过程中发挥关键作用,是SUMO修饰过程中的关键节点。越来越多的研究表明,UBC9和肿瘤的发生、发展关系密切,UBC9在许多恶性肿瘤如乳腺癌、卵巢癌中都呈高表达状态,改变癌细胞中UBC9基因的表达可导致细胞增殖及细胞周期的变化,UBC9和癌症的关系成为现在主要的研究热点之一。     

植物SUMO化修饰及其生物学功能

SUMO化修饰是细胞内蛋白质功能调节的重要方式之一。植物中的SUMO化修饰途径由SUMO分子和SUMO化酶系组成。SUMO化修饰是一个可逆的动态过程。SUMO前体蛋白在SUMO特异性蛋白酶的作用下成熟,随后通过SUMO活化酶、SUMO结合酶和SUMO连接酶将靶蛋白SUMO化,最后SUMO特异性蛋白酶将SUMO与靶蛋白分离,重新进入SUMO化循环。初步研究表明,植物SUMO化修饰参与植物花期调控、激素信号转导、抗病防御以及逆境应答等生理过程。     

植物SUMO化修饰及其生物学功能

SUMO化修饰是细胞内蛋白质功能调节的重要方式之一。植物中的SUMO化修饰途径由SUMO分子和SUMO化酶系组成。SUMO化修饰是一个可逆的动态过程。SUMO前体蛋白在SUMO特异性蛋白酶的作用下成熟, 随后通过SUMO活化酶、SUMO结合酶和SUMO连接酶将靶蛋白SUMO化, 最后SUMO特异性蛋白酶将SUMO与靶蛋白分离, 重新进入SUMO化循环。初步研究表明, 植物SUMO化修饰参与植物花期调控、激素信号转导、抗病防御以及逆境应答等生理过程。     

PIASx结构与功能的研究进展

PIAS（protein inhibitor of activated STAT）蛋白家族能够与许多蛋白质发生相互作用,其中大部分为转录因子。PIASx是4个组成成员中的一种,其包括两个亚型。PIASx通过与不同种类的蛋白相互作用,影响它们的活性和功能。PIASx蛋白的调控机制主要有两种：一种是通过其自身所具有的SUMO（smallubiquitin-related modifiers）E3连接酶活性,促进对一些转录因子、转录辅因子的SUMO化修饰,从而调控它们的转录活性;另一种是作为构架蛋白,通过与雄激素受体的作用参与雄激素介导的基因转录调节。PIAS蛋白的上述两种作用机制并不是完全互相排斥的,这体现了PIASx蛋白功能的特异性和复杂性。     

HIF-1α的可逆性SUMO化修饰

低氧诱导因子1(hypoxia inducible factor-1, HIF-1)是参与调节机体氧平衡的重要转录因子,在细胞低氧应答反应中起核心作用,能调节100多种涉及低氧应激下细胞适应和存活的靶基因．HIF-1由氧敏感的α亚基和在细胞内稳定表达的β亚基组成．其中α亚基可受到多种翻译后化学修饰作用,如在常氧下,HIF-1α通过泛素化蛋白酶修饰并导致其快速降解．最近几年发现的泛素样蛋白家族成员小泛素蛋白样修饰蛋白（SUMO）也能与HIF-1α共价结合．SUMO是一种分子量约为12 kD的小蛋白,从拟南芥到人类普遍存在．SUMO可共价结合许多靶底物蛋白,并对其进行翻译后修饰,该过程称为SUMO化．与泛素化蛋白酶体途径不同的是,SUMO化修饰能在常氧和相对低氧的条件下调节HIF-1α蛋白的稳定性,从而改变其转录活性．SUMO化是一个可逆的动态过程,可被特异性蛋白酶ULP/SENP将其从底物上去除．本文主要就HIF-1α的可逆性SUMO化修饰作一综述．     

大黄鱼ubc9基因的克隆和组织表达

类泛素化(sumoylation)是一种重要的转录后修饰过程.激活的SUMO(small ubiquitin-related modifer)和E2结合酶结合稳定后共价结合到底物上,从而完成对底物的类泛素化.UBC9(ubiquitin-conjugating enzyme)作为惟一的E2结合酶,在完成类泛素化中起着重要作用.从已构建的大黄鱼性腺线性化cDNA文库中筛选出ubc9同源片段,用SMART-RACE方法克隆得到了846 bp的全长cDNA序列.该序列编码一个由158个氨基酸组成的蛋白.该蛋白序列与已知的UBC9高度同源,含UBC保守结构域和UBC9激活位点区域.实时定量PCR分析ubc9基因在各组织器官的表达,结果发现,ubc9基因在大黄鱼的性腺中大量表达.推测UBC9在大黄鱼性腺发育中起重要的生物学作用.     

Topoisomerase I-dependent viability loss in saccharomyces cerevisiae mutants defective in both SUMO conjugation and DNA repair

Siz1 and Siz2/Nfi1 are the two Siz/PIAS SUMO E3 ligases in Saccharomyces cerevisiae. Here we show that siz1Delta siz2Delta mutants fail to grow in the absence of the homologous recombination pathway or the Fen1 ortholog RAD27. Remarkably, the growth defects of mutants such as siz1Delta siz2Delta rad52Delta are suppressed by mutations in TOP1, suggesting that these growth defects are caused by topoisomerase I activity. Other mutants that affect SUMO conjugation, including a ulp1 mutant and the nuclear pore mutants nup60Delta and nup133Delta, show similar top1-suppressible synthetic defects with DNA repair mutants, suggesting that these phenotypes also result from reduced SUMO conjugation. siz1Delta siz2Delta mutants also display TOP1-independent genome instability phenotypes, including increased mitotic recombination and elongated telomeres. We also show that SUMO conjugation, TOP1, and RAD27 have overlapping roles in telomere maintenance. Top1 is sumoylated, but Top1 does not appear to be the SUMO substrate involved in the synthetic growth defects. However, sumoylation of certain substrates, including Top1 itself and Tri1 (YMR233W), is enhanced in the absence of Top1 activity. Sumoylation is also required for growth of top1Delta cells. These results suggest that the SUMO pathway has a complex effect on genome stability that involves several mechanistically distinct processes.     

Role of SUMO/Ubc9 in DNA Damage Repair and Tumorigenesis

DNA damage repair is an important cell function for genome integrity and its deregulation can lead to genomic instability and development of malignancies. Sumoylation is an increasingly important ubiquitin-like modification of proteins affecting protein stability, enzymatic activity, nucleocytoplasmic trafficking, and protein-protein interactions. In particular, several important DNA repair enzymes are subject to sumoylation, which appears to play a role in copping with DNA damage insults. Recent reports indicate that Ubc9, the single SUMO E2 enzyme catalyzing the conjugation of SUMO to target proteins, is overexpressed in certain tumors, such as lung adenocarcinoma, ovarian carcinoma and melanoma, suggestive of its clinic significance. This review summarizes the most important DNA damage repair pathways which are potentially affected by Ubc9/SUMO and their role in regulating the function of several proteins involved in the DNA damage repair machinery.     

The SUMO pathway functions in mouse oocyte maturation

Sumoylation is an important post-translational modification in which SUMO (small ubiquitin-related modifier) proteins are bonded covalently to their substrates. Studies on the roles of sumoylation in cell cycle regulation have been emerging in both mitosis from yeast to mammals and meiosis in budding yeast, but the functions of sumoylation in mammalian meiosis, especially in oocyte meiotic maturation are not well known. Here, we examined the localization and expression of SUMO-1 and SUMO-2/3, the two basic proteins in the sumoylation pathway and investigated their roles through over-expression of Senp2 during mouse oocyte maturation. Immunofluorescent staining revealed differential patterns of SUMO-1 and SUMO-2/3 localization: SUMO-1 was localized to the spindle poles in prometaphase I, MI and MII stages, around the separating homologues in anaphase I and telophase I stages of first meiosis, while SUMO-2/3 was mainly concentrated near centromeres during mouse oocyte maturation. Immunoblot analysis uncovered the different expression profiles of SUMO-1 and SUMO-2/3 modified proteins during mouse oocyte maturation. Over-expression of Senp2, a SUMO-specific isopeptidase, caused changes of SUMO-modified proteins and led to defects in MII spindle organization in mature eggs. These results suggest that the SUMO pathway may play an indispensable role during mouse oocyte meiotic maturation.     

SUMO化修饰在NF-κB信号通路中的作用

小泛素相关修饰物（smallubiq uitin related modifier,SUMO）修饰是与泛素化修饰类似的蛋白质翻译后修饰,在细胞信号转导、核质运输与转录调控等方面发挥重要作用。核因子-κB（nuclear factor-κB,NF-κB）通路是公认的参与炎症和免疫反应的重要调节通路。近年来研究发现,SUMO通过各种机制广泛参与NF-κB信号通路的调节。研究两者的关系,可能为相关疾病的防治找到新的思路。