泛素特异性蛋白酶25(ubiquttin specific protease 25,USP25)是一种去泛素化蛋白酶,可以水解靶蛋白上的泛素,调节靶蛋白的稳定性和活性,维持蛋白质稳态。USP25在炎症反应、病毒感染、癌症、神经系统疾病、肠道系统疾病中发挥着重要的调...泛素特异性蛋白酶25(ubiquttin specific protease 25,USP25)是一种去泛素化蛋白酶,可以水解靶蛋白上的泛素,调节靶蛋白的稳定性和活性,维持蛋白质稳态。USP25在炎症反应、病毒感染、癌症、神经系统疾病、肠道系统疾病中发挥着重要的调控作用。近年来关于USP25的文献报道尚少,对USP25的深入研究仍有较大空间,本文将关于USP25的研究进展作一综述。展开更多
Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events.Balance of ubiquitination and deubiquitination has been linked to several chronic conditions,including pathologica...Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events.Balance of ubiquitination and deubiquitination has been linked to several chronic conditions,including pathological vascular remodeling.In this study,we discovered that the expression of ubiquitin-specific protease 25(USP25)is significantly up-regulated in angiotensin II(Ang II)-challenged mouse aorta.Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition(EndMT).Mechanistically,we found that USP25 interacts directly with Forkhead box O3(FOXO3)and removes the K63-linked ubiquitin chain on the K258 site of FOXO3.We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3.In addition,we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors.Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.展开更多
Background:Hepatocellular carcinoma(HCC)is one of the most common malignant tumors in the world.The ubiquitin-specific peptidase 25(USP25)protein has been reported to participate in the development of several cancers....Background:Hepatocellular carcinoma(HCC)is one of the most common malignant tumors in the world.The ubiquitin-specific peptidase 25(USP25)protein has been reported to participate in the development of several cancers.However,few studies have reported its association with HCC.In this study,we aimed to investigate the function and mechanism of USP25 in the progression of HCC.Methods:We analyzed USP25 protein expression in HCC based on The Cancer Genome Atlas(TCGA)and International Cancer Genome Consortium(ICGC)database cohorts.Then,we constructed USP25-overexpressing and USP25-knockdown HepG2,MHCC97H,and L-O2 cells.We detected the biological function of USP25 by performing a series of assays,such as Cell Counting Kit-8(CCK-8),colony formation,transwell,and wound healing assays.Western blotting and quantitative real-time polymerase chain reaction(qRT-PCR)analyses were performed to detect the interaction between USP25 and the Wnt/β-catenin signaling pathway.The relationship between USP25 and tripartite motif-containing 21(TRIM21)was assessed through mass spectrometry and co-immunoprecipitation(Co-IP)analysis.Finally,we constructed a mouse liver cancer model with the USP25 gene deletion to verify in vivo role of USP25.Results:USP25 was highly expressed in HCC tissue and HCC cell lines.Importantly,high expression of USP25 in tissues was closely related to a poor prognosis.USP25 knockdown markedly reduced the proliferation,migration,and invasion of HepG2 and MHCC97H cells,whereas USP25 overexpression led to the opposite effects.In addition,we demonstrated that USP25 interacts with TRIM21 to regulate the expression of proteins related to epithelial-mesenchymal transition(EMT;E-cadherin,N-cadherin,and Snail)and the Wnt/β-catenin pathway(β-catenin,Adenomatous polyposis coli,Axin2 and Glycogen synthase kinase 3 beta)and those of their downstream proteins(C-myc and Cyclin D1).Finally,we verified that knocking out USP25 inhibited tumor growth and distant metastasis in vivo.Conclusions:In summary,our data showed that USP25 was overexpressed in HCC.USP25 promoted the proliferation,migration,invasion,and EMT of HCC cells by interacting with TRIM21 to activate theβ-catenin signaling pathway.展开更多
目的探讨泛素蛋白连接酶E3A(ubiquitin protein ligase E3A,UBE3A)与泛素特异性蛋白酶25(ubiquitin specific protease 25,USP25)在乳腺癌组织中的表达及与临床病理特征的相关性,并分析UBE3A与USP25在乳腺癌泛素蛋白酶体系统中的关系。...目的探讨泛素蛋白连接酶E3A(ubiquitin protein ligase E3A,UBE3A)与泛素特异性蛋白酶25(ubiquitin specific protease 25,USP25)在乳腺癌组织中的表达及与临床病理特征的相关性,并分析UBE3A与USP25在乳腺癌泛素蛋白酶体系统中的关系。方法采用免疫组织化学染色检测50例乳腺癌组织及癌旁相对正常组织石蜡标本中UBE3A与USP25的表达情况,并分析它们与乳腺癌患者临床病理特征的关系;shRNA-UBE3A慢病毒转染乳腺癌MCF-7细胞,通过荧光定量PCR与Western Blot检测UBE3A基因及蛋白的敲减水平,然后观察敲减UBE3A后USP25的表达水平。结果UBE3A与USP25在乳腺癌组织中的阳性表达率分别为64%、72%,而在邻近相对正常组织中的表达均为阴性,两者在乳腺癌组织与相对正常组织中的表达差异具有统计学意义(P<0.001);UBE3A的表达与淋巴结转移(P=0.001)、Ki-67的表达(P<0.001)相关,USP25的表达与组织学分级(P=0.046)、淋巴结转移(P=0.041)、Ki-67的表达(P=0.029)相关;shRNA-UBE3A慢病毒转染乳腺癌MCF-7细胞后,UBE3A蛋白及mRNA的表达均明显降低(P<0.001),且敲减UBE3A后USP25的蛋白及mRNA的表达明显降低(P<0.001)。结论UBE3A与USP25和乳腺癌细胞的增殖、转移等生物学行为相关,在乳腺癌泛素蛋白酶体系统中UBE3A与USP25功能作用明显增强且保持动态平衡,它们可能共同作用促进乳腺癌的的发生发展。展开更多
文摘泛素特异性蛋白酶25(ubiquttin specific protease 25,USP25)是一种去泛素化蛋白酶,可以水解靶蛋白上的泛素,调节靶蛋白的稳定性和活性,维持蛋白质稳态。USP25在炎症反应、病毒感染、癌症、神经系统疾病、肠道系统疾病中发挥着重要的调控作用。近年来关于USP25的文献报道尚少,对USP25的深入研究仍有较大空间,本文将关于USP25的研究进展作一综述。
基金supported by the National Natural Science Foundation of China(82370244 to Yi Wang,82361138563 to Yi Wang,and 82271347 to Gaojun Wu)Natural Science Foundation of Zhejiang Province(LY22H070004 to Wu Luo)Wenzhou City Research Project(ZY2020016 to Gaojun Wu).
文摘Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events.Balance of ubiquitination and deubiquitination has been linked to several chronic conditions,including pathological vascular remodeling.In this study,we discovered that the expression of ubiquitin-specific protease 25(USP25)is significantly up-regulated in angiotensin II(Ang II)-challenged mouse aorta.Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition(EndMT).Mechanistically,we found that USP25 interacts directly with Forkhead box O3(FOXO3)and removes the K63-linked ubiquitin chain on the K258 site of FOXO3.We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3.In addition,we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors.Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.
基金National Natural Science Foundation of China(No.81870392)
文摘Background:Hepatocellular carcinoma(HCC)is one of the most common malignant tumors in the world.The ubiquitin-specific peptidase 25(USP25)protein has been reported to participate in the development of several cancers.However,few studies have reported its association with HCC.In this study,we aimed to investigate the function and mechanism of USP25 in the progression of HCC.Methods:We analyzed USP25 protein expression in HCC based on The Cancer Genome Atlas(TCGA)and International Cancer Genome Consortium(ICGC)database cohorts.Then,we constructed USP25-overexpressing and USP25-knockdown HepG2,MHCC97H,and L-O2 cells.We detected the biological function of USP25 by performing a series of assays,such as Cell Counting Kit-8(CCK-8),colony formation,transwell,and wound healing assays.Western blotting and quantitative real-time polymerase chain reaction(qRT-PCR)analyses were performed to detect the interaction between USP25 and the Wnt/β-catenin signaling pathway.The relationship between USP25 and tripartite motif-containing 21(TRIM21)was assessed through mass spectrometry and co-immunoprecipitation(Co-IP)analysis.Finally,we constructed a mouse liver cancer model with the USP25 gene deletion to verify in vivo role of USP25.Results:USP25 was highly expressed in HCC tissue and HCC cell lines.Importantly,high expression of USP25 in tissues was closely related to a poor prognosis.USP25 knockdown markedly reduced the proliferation,migration,and invasion of HepG2 and MHCC97H cells,whereas USP25 overexpression led to the opposite effects.In addition,we demonstrated that USP25 interacts with TRIM21 to regulate the expression of proteins related to epithelial-mesenchymal transition(EMT;E-cadherin,N-cadherin,and Snail)and the Wnt/β-catenin pathway(β-catenin,Adenomatous polyposis coli,Axin2 and Glycogen synthase kinase 3 beta)and those of their downstream proteins(C-myc and Cyclin D1).Finally,we verified that knocking out USP25 inhibited tumor growth and distant metastasis in vivo.Conclusions:In summary,our data showed that USP25 was overexpressed in HCC.USP25 promoted the proliferation,migration,invasion,and EMT of HCC cells by interacting with TRIM21 to activate theβ-catenin signaling pathway.
文摘目的探讨泛素蛋白连接酶E3A(ubiquitin protein ligase E3A,UBE3A)与泛素特异性蛋白酶25(ubiquitin specific protease 25,USP25)在乳腺癌组织中的表达及与临床病理特征的相关性,并分析UBE3A与USP25在乳腺癌泛素蛋白酶体系统中的关系。方法采用免疫组织化学染色检测50例乳腺癌组织及癌旁相对正常组织石蜡标本中UBE3A与USP25的表达情况,并分析它们与乳腺癌患者临床病理特征的关系;shRNA-UBE3A慢病毒转染乳腺癌MCF-7细胞,通过荧光定量PCR与Western Blot检测UBE3A基因及蛋白的敲减水平,然后观察敲减UBE3A后USP25的表达水平。结果UBE3A与USP25在乳腺癌组织中的阳性表达率分别为64%、72%,而在邻近相对正常组织中的表达均为阴性,两者在乳腺癌组织与相对正常组织中的表达差异具有统计学意义(P<0.001);UBE3A的表达与淋巴结转移(P=0.001)、Ki-67的表达(P<0.001)相关,USP25的表达与组织学分级(P=0.046)、淋巴结转移(P=0.041)、Ki-67的表达(P=0.029)相关;shRNA-UBE3A慢病毒转染乳腺癌MCF-7细胞后,UBE3A蛋白及mRNA的表达均明显降低(P<0.001),且敲减UBE3A后USP25的蛋白及mRNA的表达明显降低(P<0.001)。结论UBE3A与USP25和乳腺癌细胞的增殖、转移等生物学行为相关,在乳腺癌泛素蛋白酶体系统中UBE3A与USP25功能作用明显增强且保持动态平衡,它们可能共同作用促进乳腺癌的的发生发展。
