Stress granules(Sgs)are membraneless cytoplasmic condensates that dynamically assemble in response to various stressors and reversibly disassemble after stimulus removal;however,the mechanisms underlying Sg dynamics a...
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Stress granules(Sgs)are membraneless cytoplasmic condensates that dynamically assemble in response to various stressors and reversibly disassemble after stimulus removal;however,the mechanisms underlying Sg dynamics and their physiological roles in germ cell development are ***,we show that SERbp1(SERPINE1 mRNA binding protein 1)is a universal Sg component and conserved regulator of Sg clearance in somatic and male germ ***1 interacts with the Sg core component g3bp1 and 26S proteasome proteins PSMD10 and PSMA3 and recruits them to *** the absence of SERbp1,reduced 20S proteasome activity,mislocalized valosin containing protein(VCP)and Fas associated factor family member 2(FAF2),and diminished K63-linked polyubiquitination of g3bp1 during the Sg recovery period were ***,the depletion of SERbp1 in testicular cells in vivo causes increased germ cell apoptosis upon scrotal heat ***,we propose that a SERbp1-mediated mechanism regulates 26S proteasome activity and g3bp1 ubiquitination to facilitate Sg clearance in both somatic and germ cell lines.
BACKgROUND The increased expression of g3bp1 was positively correlated with the prognosis of liver *** To investigate the effect of g3bp1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver failure(...
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BACKgROUND The increased expression of g3bp1 was positively correlated with the prognosis of liver *** To investigate the effect of g3bp1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver failure(ACLF)after the treatment of artificial liver support system(ALSS).METHODS A total of 244 patients with ALF and ACLF were enrolled in this *** levels of g3bp1 on admission and at discharge were *** validation set of 514 patients was collected to verify the predicted effect of g3bp1 and the viability of *** This study was shown that lactate dehydrogenase(LDH),alpha-fetoprotein(AFP)and prothrombin time were closely related to the prognosis of *** the ALSS treatment,the patient’amount of decreased g3bp1 index in difference of g3bp1 between the value of discharge and admission(difg3bp1)group had a nearly 10-fold increased risk of progression compared with the amount of increased g3bp1 *** subgroup analysis showed that the difg3bp1group had a higher risk of progression,regardless of model for end-stage liver disease high-risk or low-risk *** the same time,compared with the inflam matory marks[tumor necrosis factor-α,interleukin(IL)-1βand IL-18],g3bp1 had higher discrimination and was more stable in the model analysis and validation *** combined with AFP and LDH,concordance index was respectively 0.84 and 0.8 in training and validation *** This study indicated that g3bp1 could predict the prognosis of ALF or ACLF patients treated with *** combination of g3bp1,AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.
目的研究g3bp1(Ras-gTPase-activating protein SH3 domain binding protein 1)在宫颈癌组织中的表达情况,分析g3bp1的表达水平及其相关临床意义。方法利用公开的gEO宫颈癌数据集分析g3bp1的mRNA水平在癌和癌旁组织的表达差异情况;取30...
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目的研究g3bp1(Ras-gTPase-activating protein SH3 domain binding protein 1)在宫颈癌组织中的表达情况,分析g3bp1的表达水平及其相关临床意义。方法利用公开的gEO宫颈癌数据集分析g3bp1的mRNA水平在癌和癌旁组织的表达差异情况;取306例宫颈癌组织制作组织芯片,通过免疫组织化学检测癌组织中g3bp1的表达水平,统计分析g3bp1在宫颈癌中与正常宫颈组织和鳞状上皮内病变组织的表达差异情况,分析宫颈癌组织中g3bp1的表达与患者临床病理资料的相关性及对患者生存预后的影响。结果在gSE6791、gSE7803和gSE7410数据集中,我们发现g3bp1的mRNA水平在宫颈癌组织中的表达显著高于癌旁组织。免疫组织化学检测结果显示g3bp1的蛋白表达随着宫颈鳞状上皮内病变和宫颈癌的发生有逐渐增高的趋势。免疫组织化学和χ2检验结果显示g3bp1高表达与年龄、肿瘤大小、肿瘤分化、肌层浸润、阴道浸润、盆腔淋巴结转移、FIgO分期以及不良预后相关。Cox多因素分析显示g3bp1高表达是该批宫颈癌患者的独立危险预后因素。通过与g3bp1的表达水平整合可以显著促进FIgO分期在判断宫颈癌患者预后中的准确性。结论g3bp1高表达可能是宫颈癌患者的独立危险预后因素,并可能参与宫颈癌的发生发展等进程。
g3bp1 is the nucleating protein of stress-induced liquid-liquid phase separation(LLPS).Here,we found that the RNA recognition motif(RRM) domain of g3bp1 facilitates LLPS of the Rgg *** methylation catalyzed by PR...
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g3bp1 is the nucleating protein of stress-induced liquid-liquid phase separation(LLPS).Here,we found that the RNA recognition motif(RRM) domain of g3 bp1 facilitates LLPS of the Rgg *** methylation catalyzed by PRMT1 suppressed the phase separation of g3 bp1 RRM-Rgg,which is promoted by the addition of total *** RNA binding topology was hence mapped by using NMR chemical shift perturbations of the 15 N-labeled g3 bp1 RRM-Rgg upon titration of various RNA sequences,e.g.,poly(A),poly(C),poly(U) and *** reversible formation of g3 bp1 foci was observed in *** upon treatment of heat *** are currently working on the regulatory roles of arginine methylation in the assembly of heat-induced g3 bp 1 stress granule.
研究背景:乳腺癌是女性最常见的恶性肿瘤,中国乳腺癌的发病率逐年上升,并且与西方国家相比存在年轻化、分期晚的特点。Ras信号传导通路在细胞增殖、分化等重要生物学功能中发挥作用。Ras途径的异常活化是促使肿瘤发生发展的主要机制之一。g3bp1(Ras-gTPase-activating protein SH3 domain-binding protein 1)是Ras活性的负反馈调节因子-Ras gTP酶活化蛋白SH3结构域的特异结合蛋白,是Ras信号传导通路中重要的调控分子和下游靶分子。研究发现,g3bp1在多种肿瘤组织和细胞中高表达,并且能够通过多种信号传导途径参与调节肿瘤的增殖、侵袭。最近的研究发现,g3bp1在乳腺癌细胞系中表达升高,并参与调控乳腺癌细胞的上皮-间质转化以及促进癌细胞的增殖、迁移[7],然而g3bp1在乳腺癌组织中的表达及临床意义尚不清楚。因此,本研究中,我们首先通过基因数据库的检索分析初步探讨g3bp1在乳腺癌中的表达及临床意义,然后利用免疫组织化学和Western blot等方法,进一步探究真实世界中g3bp1在乳腺癌组织标本和乳腺癌细胞系中的表达及其临床意义。方法:1.利用TCgA、Oncomine、gEO和Kmplot数据库分析g3bp1在乳腺癌中的表达、g3bp1与乳腺癌内分泌耐药、g3bp1与乳腺癌预后之间的相关性。2.采用免疫组化技术进一步验证g3bp1在乳腺癌中组织标本中的表达情况,同时收集乳腺癌标本对应患者的临床信息,进而分析g3bp1与乳腺癌临床病理特征的关系。3.采用Western blot检测g3bp1在乳腺癌不同细胞系中的表达,观察g3bp1在不同分型乳腺癌细胞系中的表达差异。结果:***和Oncomine数据库分析结果显示:g3bp1 m RNA在乳腺癌组织中的表达水平高于正常乳腺组织(Pg3bp1 m RNA在Luminal型乳腺癌中的表达水平高于三阴型(Pg3bp1 m RNA的表达差异无统计学意义。***数据库分析结果显示:他莫昔芬耐药细胞株的g3bp1 m RNA表达水平明显高于敏感细胞株(Pg3bp1 m RNA高表达组患者的无复发生存期明显低于低表达组(HR=1.43,Pg3bp1 m RNA表达与OS无显著相关(HR=1.09,P=0.45)。5.90例乳腺癌组织蜡块免疫组化染色结果显示:g3bp1蛋白在乳腺癌组织中的阳性表达率高于癌旁组织(Pg3bp1蛋白在不同分子分型乳腺癌组织中的表达水平存在差异,其中在Luminal B型(包括Luminal B(HER-2阴性)型和Luminal B型(HER-2阳性))乳腺癌中的阳性表达率最高,在三阴型乳腺癌中的表达率最低。进一步将Luminal A型、Luminal B型合并为Luminal型乳腺癌,发现g3bp1蛋白在Luminal型乳腺癌中的阳性表达率高于三阴型(Pg3bp1蛋白表达水平高于MDA-MB-231(ER-,PR-,HER2-)细胞,差异具有统计学意义(Pg3bp1蛋白表达的相关性,结果显示:g3bp1表达与ER、PR的表达呈正相关(r=0.303,P0.05)。结论:g3bp1在乳腺癌中表达升高,并且在Luminal型乳腺癌中的阳性表达率高于三阴型,基因数据库分析g3bp1的表达与乳腺癌的疾病复发时间可能有关,g3bp1的表达可能成为乳腺癌诊断、分子分型及病情预测的新型标记物。
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