泛素蛋白酶体途径(Alterations in the ubiquitin-proteasome system UPS),是由泛素介导的一种高度复杂的蛋白降解系统,普遍参与各种生物学功能,例如细胞生长,细胞周期进程,DNA转录、损伤、修复和信号转导及自噬,因此在体内各种调节蛋...泛素蛋白酶体途径(Alterations in the ubiquitin-proteasome system UPS),是由泛素介导的一种高度复杂的蛋白降解系统,普遍参与各种生物学功能,例如细胞生长,细胞周期进程,DNA转录、损伤、修复和信号转导及自噬,因此在体内各种调节蛋白的降解和整体细胞的稳态中发挥着至关重要的作用。UPS的表达功能异常或改变可能导致蛋白质的积累,与人类多种疾病相关,包括恶性肿瘤、血液系统疾病等。其中泛素化是泛素蛋白酶体系统途径的关键步骤,PSMD2 (proteasome 26S subunit, non-ATPase 14)位于蛋白酶体26S亚基,是一种非ATP酶组分,是泛素–蛋白酶体的重要组成部分之一。近年来,其在疾病发生发展中的作用越来越受到关注,本文将对PSMD2的结构、作用机制及在不同疾病中的研究进展进行综述。展开更多
The proteasome,an evolutionarily conserved proteolytic complex comprising the 20S core particle and 19S regulatory particles,performs both shared and distinct functions across various tissues and organs.Spermatogenesi...The proteasome,an evolutionarily conserved proteolytic complex comprising the 20S core particle and 19S regulatory particles,performs both shared and distinct functions across various tissues and organs.Spermatogenesis,a highly complex developmental process,relies on proteasome activity at multiple stages to regulate protein turnover.In this study,we selected the 20S subunit PSMA1 and 19S regulatory subunit PSMD2 to investigate the potential functions of the proteasome in spermatogenesis.Using Psma1-EGFP and Psmd2-mCherry knock-in mouse models,we confirmed the expression of both subunits in all spermatogenic cell types,with pronounced presence in early germ cell development.To further clarify their functional significance,we specifically knocked out Psma1 and Psmd2 in germ cells.Deletion of either PSMA1 or PSMD2 led to disrupted spermatogenesis,characterized by the complete absence of sperm in the epididymis.Subsequent analysis indicated that loss of these proteasome components impaired meiotic initiation.Psma1 and Psmd2 knockout germ cells showed accumulation of DMRT1,a key regulator of mitosis-to-meiosis transition,leading to a reduction in STRA8 levels and consequent disruption of meiosis initiation.This study sheds light on the molecular mechanisms that govern meiotic initiation and identifies potential genes associated with male infertility.展开更多
The infection of host plants by many different viruses causes reactive oxygen species(Ros)accumulation and yellowing symptoms,but the mechanisms through which plant viruses counteract RoS-mediated immunity to facilita...The infection of host plants by many different viruses causes reactive oxygen species(Ros)accumulation and yellowing symptoms,but the mechanisms through which plant viruses counteract RoS-mediated immunity to facilitate infection and symptom development have not been fully elucidated.Most plant viruses are transmitted by insect vectors in the field,but the molecular mechanisms underlying virus-host-insect interactions are unclear.In this study,we investigated the interactions among wheat,barley yellow dwarf virus(BYDV),and its aphid vector and found that the BYDV movement protein(MP)interacts with both wheat catalases(CATs)and the 26S proteasomeubiquitin receptor non-ATPase regulatorysubunit2homolog(PSMD2)to facilitate the 26S proteasome-mediateddegradation of CATs,promotingviral infection,disease symptom development,and aphid transmission.Overexpression of the BYDV MP gene in wheat enhanced the degradation of CATs,which leading to increased accumulation of ROS and thereby enhanced viral infection.Interestingly,transgenic wheat lines overexpressing BYDV MP showed significantly reduced proliferation of wingless aphids and an increased number of winged aphids.Consistent with this observation,silencing of CAT genes also enhanced viral accumulation and reduced the proliferation of wingless aphids but increased the occurrence of winged aphids.In contrast,transgenic wheat plants overexpressing TaCAT1 exhibited the opposite changes and showed increases in grain size and weight upon infection with BYDV.Biochemical assays demonstrated that BYDV MP interacts with PSMD2 and promotes 26S proteasome-mediated degradation of TaCAT1 likely in a ubiquitination-independent manner.Collectively,our study reveals a molecular mechanism by which a plant virus manipulates the Ros production system of host plants to facilitate viral infection and transmission,shedding new light on the sophisticated interactions among viruses,host plants,and insect vectors.展开更多
文摘泛素蛋白酶体途径(Alterations in the ubiquitin-proteasome system UPS),是由泛素介导的一种高度复杂的蛋白降解系统,普遍参与各种生物学功能,例如细胞生长,细胞周期进程,DNA转录、损伤、修复和信号转导及自噬,因此在体内各种调节蛋白的降解和整体细胞的稳态中发挥着至关重要的作用。UPS的表达功能异常或改变可能导致蛋白质的积累,与人类多种疾病相关,包括恶性肿瘤、血液系统疾病等。其中泛素化是泛素蛋白酶体系统途径的关键步骤,PSMD2 (proteasome 26S subunit, non-ATPase 14)位于蛋白酶体26S亚基,是一种非ATP酶组分,是泛素–蛋白酶体的重要组成部分之一。近年来,其在疾病发生发展中的作用越来越受到关注,本文将对PSMD2的结构、作用机制及在不同疾病中的研究进展进行综述。
基金supported by the National Science Fund for Distinguished Young Scholars (81925015)Science and Technology Project of Guangzhou (2023A03J0886,2023A03J0871)National Natural Science Foundation of China (82030039,32400709)。
文摘The proteasome,an evolutionarily conserved proteolytic complex comprising the 20S core particle and 19S regulatory particles,performs both shared and distinct functions across various tissues and organs.Spermatogenesis,a highly complex developmental process,relies on proteasome activity at multiple stages to regulate protein turnover.In this study,we selected the 20S subunit PSMA1 and 19S regulatory subunit PSMD2 to investigate the potential functions of the proteasome in spermatogenesis.Using Psma1-EGFP and Psmd2-mCherry knock-in mouse models,we confirmed the expression of both subunits in all spermatogenic cell types,with pronounced presence in early germ cell development.To further clarify their functional significance,we specifically knocked out Psma1 and Psmd2 in germ cells.Deletion of either PSMA1 or PSMD2 led to disrupted spermatogenesis,characterized by the complete absence of sperm in the epididymis.Subsequent analysis indicated that loss of these proteasome components impaired meiotic initiation.Psma1 and Psmd2 knockout germ cells showed accumulation of DMRT1,a key regulator of mitosis-to-meiosis transition,leading to a reduction in STRA8 levels and consequent disruption of meiosis initiation.This study sheds light on the molecular mechanisms that govern meiotic initiation and identifies potential genes associated with male infertility.
基金supported by grants to Y.Wu and L.Z.from the Shaanxi Key Research and Development Program(No.2022KWZ-11)the Ministry of Science and Technology Plans to Introduce High-End Foreign Experts(G2022172015L)the National Natural Science Foundation of China(Nos.32372501 and 31701761).
文摘The infection of host plants by many different viruses causes reactive oxygen species(Ros)accumulation and yellowing symptoms,but the mechanisms through which plant viruses counteract RoS-mediated immunity to facilitate infection and symptom development have not been fully elucidated.Most plant viruses are transmitted by insect vectors in the field,but the molecular mechanisms underlying virus-host-insect interactions are unclear.In this study,we investigated the interactions among wheat,barley yellow dwarf virus(BYDV),and its aphid vector and found that the BYDV movement protein(MP)interacts with both wheat catalases(CATs)and the 26S proteasomeubiquitin receptor non-ATPase regulatorysubunit2homolog(PSMD2)to facilitate the 26S proteasome-mediateddegradation of CATs,promotingviral infection,disease symptom development,and aphid transmission.Overexpression of the BYDV MP gene in wheat enhanced the degradation of CATs,which leading to increased accumulation of ROS and thereby enhanced viral infection.Interestingly,transgenic wheat lines overexpressing BYDV MP showed significantly reduced proliferation of wingless aphids and an increased number of winged aphids.Consistent with this observation,silencing of CAT genes also enhanced viral accumulation and reduced the proliferation of wingless aphids but increased the occurrence of winged aphids.In contrast,transgenic wheat plants overexpressing TaCAT1 exhibited the opposite changes and showed increases in grain size and weight upon infection with BYDV.Biochemical assays demonstrated that BYDV MP interacts with PSMD2 and promotes 26S proteasome-mediated degradation of TaCAT1 likely in a ubiquitination-independent manner.Collectively,our study reveals a molecular mechanism by which a plant virus manipulates the Ros production system of host plants to facilitate viral infection and transmission,shedding new light on the sophisticated interactions among viruses,host plants,and insect vectors.
