The nucleolus,as the‘nucleus of the nucleus’,is a prominent subcellular organelle in a eukaryocyte.The nucleolus serves as the centre for ribosome biogenesis,as well as an important site for cell-cycle regulation,ce...The nucleolus,as the‘nucleus of the nucleus’,is a prominent subcellular organelle in a eukaryocyte.The nucleolus serves as the centre for ribosome biogenesis,as well as an important site for cell-cycle regulation,cellular senescence,and stress response.The protein composition of the nucleolus changes dynamically through protein turnover to meet the needs of cellular activities or stress responses.Recent studies have identified a nucleolus-localized protein degradation pathway in zebrafish and humans,namely the Def-CAPN3 pathway,which is essential to ribosome production and cell-cycle progression,by controlling the turnover of multiple substrates(e.g.,ribosomal small-subunit[SSU]processome component Mpp10,transcription factor p53,check-point proteins Chk1 and Wee1).This pathway relies on the Ca2þ-dependent cysteine proteinase CAPN3 and is independent of the ubiquitin-mediated proteasome pathway.CAPN3 is recruited by nucleolar protein Def from cytoplasm to nucleolus,where it proteolyzes its substrates which harbor a CAPN3 recognition-motif.Def depletion leads to the exclusion of CAPN3 and accumulation of p53,Wee1,Chk1,and Mpp10 in the nucleolus that result in cell-cycle arrest and rRNA processing abnormality.Here,we summarize the discovery of the Def-CAPN3 pathway and propose its biological role in cell-cycle control and ribosome biogenesis.展开更多
Nuclear bodies have long been noted in interphase nuclei of plant cells, but their structural component, origin and function are still unclear by now. The present work showed in onion cells the nuclear bodies appeared...Nuclear bodies have long been noted in interphase nuclei of plant cells, but their structural component, origin and function are still unclear by now. The present work showed in onion cells the nuclear bodies appeared as a spherical structure about 0.3 to 0.8 microm in diameter. They possibly were formed in nucleolus and subsequently released, and entered into nucleoplasm. Observation through cytochemical staining method at the ultrastructural level confirmed that nuclear bodies consisted of ribonucleoproteins (RNPs) and silver-stainable proteins. Immunocytochemical results revealed that nuclear bodies contained no DNA and ribosomal gene transcription factor (UBF). Based on these data, we suggested that nuclear bodies are not related to the ribosome or other gene transcription activities, instead they may act as subnuclear structures for RNPs transport from nucleolus to cytoplasm, and may also be involved in splicing of pre-mRNAs.展开更多
[目的]探讨乳腺癌组织中核仁纺缍体相关蛋白1 (nucleolus spinosa-related protein 1,NuSAP1)的表达与腋窝淋巴结转移的关系。[方法]采用免疫组织化学染色法检测100例乳腺癌组织(浸润性导管癌)及其配对的癌旁组织(距离肿瘤边缘>3cm)...[目的]探讨乳腺癌组织中核仁纺缍体相关蛋白1 (nucleolus spinosa-related protein 1,NuSAP1)的表达与腋窝淋巴结转移的关系。[方法]采用免疫组织化学染色法检测100例乳腺癌组织(浸润性导管癌)及其配对的癌旁组织(距离肿瘤边缘>3cm)中NuSAP1、Hedgehog信号通路相关蛋白(Smo和Gli-1)表达水平。采用Logistic多因素分析影响乳腺癌腋窝淋巴结转移的影响因素。[结果]乳腺癌组织中NuSAP1高表达率为65%(65/100),明显高于癌旁组织的18%(18/100)(χ2=45.945,P<0.001)。NuSAP1高表达组中WHO分级Ⅲ级、TNMⅢ期、腋窝淋巴结转移率均高于低表达组(P<0.05)。WHO分级Ⅲ级(OR=1.689,95%CI:1.240~3.333)、TNMⅢ期(OR=1.543,95%CI:1.345~3.602)、三阴性乳腺癌(OR=2.786,95%CI:1.764~4.002)和NuSAP1高表达(OR=2.507,95%CI:1.684~3.971)是乳腺癌患者腋窝淋巴结转移的独立影响因素(P<0.05)。NuSAP1表达水平与腋窝淋巴结转移数目呈正相关(r=0.561,P<0.001)。NuSAP1表达与Smo、Gli-1表达水平呈正相关(r分别为0.748和0.528,P均<0.001)。[结论] NuSAP1可能通过激活Hedgehog信号通路参与腋窝淋巴结的转移。展开更多
基金the National Key R&D Program of China and the Natural Science Foundation of China in the order of 2018YFA0800502,2017YFA0504501,31330050.
文摘The nucleolus,as the‘nucleus of the nucleus’,is a prominent subcellular organelle in a eukaryocyte.The nucleolus serves as the centre for ribosome biogenesis,as well as an important site for cell-cycle regulation,cellular senescence,and stress response.The protein composition of the nucleolus changes dynamically through protein turnover to meet the needs of cellular activities or stress responses.Recent studies have identified a nucleolus-localized protein degradation pathway in zebrafish and humans,namely the Def-CAPN3 pathway,which is essential to ribosome production and cell-cycle progression,by controlling the turnover of multiple substrates(e.g.,ribosomal small-subunit[SSU]processome component Mpp10,transcription factor p53,check-point proteins Chk1 and Wee1).This pathway relies on the Ca2þ-dependent cysteine proteinase CAPN3 and is independent of the ubiquitin-mediated proteasome pathway.CAPN3 is recruited by nucleolar protein Def from cytoplasm to nucleolus,where it proteolyzes its substrates which harbor a CAPN3 recognition-motif.Def depletion leads to the exclusion of CAPN3 and accumulation of p53,Wee1,Chk1,and Mpp10 in the nucleolus that result in cell-cycle arrest and rRNA processing abnormality.Here,we summarize the discovery of the Def-CAPN3 pathway and propose its biological role in cell-cycle control and ribosome biogenesis.
文摘Nuclear bodies have long been noted in interphase nuclei of plant cells, but their structural component, origin and function are still unclear by now. The present work showed in onion cells the nuclear bodies appeared as a spherical structure about 0.3 to 0.8 microm in diameter. They possibly were formed in nucleolus and subsequently released, and entered into nucleoplasm. Observation through cytochemical staining method at the ultrastructural level confirmed that nuclear bodies consisted of ribonucleoproteins (RNPs) and silver-stainable proteins. Immunocytochemical results revealed that nuclear bodies contained no DNA and ribosomal gene transcription factor (UBF). Based on these data, we suggested that nuclear bodies are not related to the ribosome or other gene transcription activities, instead they may act as subnuclear structures for RNPs transport from nucleolus to cytoplasm, and may also be involved in splicing of pre-mRNAs.