Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive condition associated with exocrine pancreatic insufficiency,and is characterized by hypoplastic nasal alae,mental retardation,sensorineural hearing loss,s...Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive condition associated with exocrine pancreatic insufficiency,and is characterized by hypoplastic nasal alae,mental retardation,sensorineural hearing loss,short stature,scalp defects,dental abnormalities and abnormal hair patterns. Growth hormone deficiency,hypopituitarism,and impaired glucagon secretion response to insulin-induced hypoglycemia have been reported. Congenital heart defects have also been described in this condition. Mental retardation is typically moderate to severe in patients with JBS; however,normal intelligence can occur. In the pancreas,there is a selective defect of acinar tissue,whereas the islets of Langerhans and ducts are preserved. Diabetes has been reported in older children,suggesting the progressive nature of pancreatic disease. The molecular basis of JBS has recently been mapped to chromosome 15q15-q21 with identified mutations in the UBR1 gene. We report the case of a 7-year-old female with pancreatic insufficiency and mild phenotypic features,in whom the diagnosis of JBS was established using recently described molecular testing for the UBR1 gene.展开更多
Objective UBR5,recently identified as a potential target for cancer therapeutics,is overexpressed in multiple malignant tumors.In addition,it is closely associated with the growth,prognosis,metastasis,and treatment re...Objective UBR5,recently identified as a potential target for cancer therapeutics,is overexpressed in multiple malignant tumors.In addition,it is closely associated with the growth,prognosis,metastasis,and treatment response of multiple types of cancer.Although emerging evidence supports the relationship between UBR5 and cancer,there are limited cancer analyses available.Methods In this study,online databases(TIMER2,GEPIA2,UALCAN,c-BioPortal,STRING)were employed to comprehensively explore expression levels and prognostic values of the UBR5 gene in cancer,using bioinformatic methods.Results We found that various characteristics of the UBR5 gene such as gene expression,survival value,genetic mutation,protein phosphorylation,immune infiltration,and pathway activities in the normal tissue were remarkably different from those in the primary tumor.Furthermore,“protein processing in spliceosome”and“ubiquitin mediated proteolysis”have provided evidence for their potential involvement in the development of cancer.Conclusion Our findings may provide insights for the selection of novel immunotherapeutic targets and prognostic biomarkers for cancer.展开更多
Metastasis accounts for the major cause of colorectal cancer(CRC)related mortality due to the lack of effective treatments.In this study,we integrated the single-cell RNA-seq(sc RNA-seq)and bulk RNA-seq data and ident...Metastasis accounts for the major cause of colorectal cancer(CRC)related mortality due to the lack of effective treatments.In this study,we integrated the single-cell RNA-seq(sc RNA-seq)and bulk RNA-seq data and identified the transcriptional coactivator SUB1 homolog(SacSaccharomyces cerevisiae)/PC4(positive cofactor 4)associated with CRC metastasis.Elevated SUB1 expression was correlated with advanced tumor stage and poor survival in CRC.In vivo and vitro assays showed that SUB1 depletion could inhibit the invasive and metastatic abilities of CRC cells.SUB1 activated NF-κB signaling and its transcriptional target genes CXCL1 and CXCL3 to drive CRC metastasis.Mechanistically,SUB1 integrated with the E3 ubiquitin-protein ligase UBR5 and increased its protein level in CRC cells.Subsequently,the increased UBR5mainly mediated Lys11-linked polyubiquitination and degradation of NF-κB negative regulator UBXN1,thus to activate the NF-κB signaling.Overall,our study demonstrated that SUB1 promoted CRC progression by modulating UBR5/UBXN1 and activating NF-κB signaling,providing a new therapeutic strategy for treating metastatic CRC through targeting SUB1.展开更多
Plant height is an important agronomic trait for lodging resistance and yield.Here,we report a new plantheight-related gene,OsUBR7 in rice(Oryza sativa L.);knockout of OsUBR7 caused fewer cells in internodes,resulting...Plant height is an important agronomic trait for lodging resistance and yield.Here,we report a new plantheight-related gene,OsUBR7 in rice(Oryza sativa L.);knockout of OsUBR7 caused fewer cells in internodes,resulting in a semi-dwarf phenotype.OsUBR7 encodes a putative E3 ligase containing a plant homeodomain finger and a ubiquitin protein ligase E3 component N-recognin 7(UBR7)domain.OsUBR7 interacts with histones and monoubiquitinates H2B(H2Bub1)at lysine148 in coordination with the E2 conjugase OsUBC18.OsUBR7 mediates H2Bub1 at a number of chromatin loci for the normal expression of target genes,including cell-cycle-related and pleiotropic genes,consistent with the observation that cell-cycle progression was suppressed in the osubr7 mutant owing to reductions in H2Bub1 and expression levels at these loci.The genetic divergence of OsUBR7 alleles among japonica and indica cultivars affects their transcriptional activity,and these alleles may have undergone selection during rice domestication.Overall,our results reveal a novel mechanism that mediates H2Bub1 in plants,and UBR7 orthologs could be utilized as an untapped epigenetic resource for crop improvement.展开更多
基金Supported by Grant from the German Research Foundation (DFG) to MZ
文摘Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive condition associated with exocrine pancreatic insufficiency,and is characterized by hypoplastic nasal alae,mental retardation,sensorineural hearing loss,short stature,scalp defects,dental abnormalities and abnormal hair patterns. Growth hormone deficiency,hypopituitarism,and impaired glucagon secretion response to insulin-induced hypoglycemia have been reported. Congenital heart defects have also been described in this condition. Mental retardation is typically moderate to severe in patients with JBS; however,normal intelligence can occur. In the pancreas,there is a selective defect of acinar tissue,whereas the islets of Langerhans and ducts are preserved. Diabetes has been reported in older children,suggesting the progressive nature of pancreatic disease. The molecular basis of JBS has recently been mapped to chromosome 15q15-q21 with identified mutations in the UBR1 gene. We report the case of a 7-year-old female with pancreatic insufficiency and mild phenotypic features,in whom the diagnosis of JBS was established using recently described molecular testing for the UBR1 gene.
基金Supported by grants from the Guangxi Natural Science Foundation(No.2019GXNSFBA245032)the Guangxi Science and Technology Plan Project(No.Gui Ke AD20238021)+2 种基金the open funds of the Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation(No.203030302008,203030302018 and 2020KF010)Guilin Science Research and Technology Development Project(No.20190218-5-5)the Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi(No.2021KY0496).
文摘Objective UBR5,recently identified as a potential target for cancer therapeutics,is overexpressed in multiple malignant tumors.In addition,it is closely associated with the growth,prognosis,metastasis,and treatment response of multiple types of cancer.Although emerging evidence supports the relationship between UBR5 and cancer,there are limited cancer analyses available.Methods In this study,online databases(TIMER2,GEPIA2,UALCAN,c-BioPortal,STRING)were employed to comprehensively explore expression levels and prognostic values of the UBR5 gene in cancer,using bioinformatic methods.Results We found that various characteristics of the UBR5 gene such as gene expression,survival value,genetic mutation,protein phosphorylation,immune infiltration,and pathway activities in the normal tissue were remarkably different from those in the primary tumor.Furthermore,“protein processing in spliceosome”and“ubiquitin mediated proteolysis”have provided evidence for their potential involvement in the development of cancer.Conclusion Our findings may provide insights for the selection of novel immunotherapeutic targets and prognostic biomarkers for cancer.
基金supported by the National Natural Science Foundation of China(82073229,82072623)。
文摘Metastasis accounts for the major cause of colorectal cancer(CRC)related mortality due to the lack of effective treatments.In this study,we integrated the single-cell RNA-seq(sc RNA-seq)and bulk RNA-seq data and identified the transcriptional coactivator SUB1 homolog(SacSaccharomyces cerevisiae)/PC4(positive cofactor 4)associated with CRC metastasis.Elevated SUB1 expression was correlated with advanced tumor stage and poor survival in CRC.In vivo and vitro assays showed that SUB1 depletion could inhibit the invasive and metastatic abilities of CRC cells.SUB1 activated NF-κB signaling and its transcriptional target genes CXCL1 and CXCL3 to drive CRC metastasis.Mechanistically,SUB1 integrated with the E3 ubiquitin-protein ligase UBR5 and increased its protein level in CRC cells.Subsequently,the increased UBR5mainly mediated Lys11-linked polyubiquitination and degradation of NF-κB negative regulator UBXN1,thus to activate the NF-κB signaling.Overall,our study demonstrated that SUB1 promoted CRC progression by modulating UBR5/UBXN1 and activating NF-κB signaling,providing a new therapeutic strategy for treating metastatic CRC through targeting SUB1.
基金supported by the Major Program of Guangdong Basic and Applied Basic Research(2019B030302006)the National Natural Science Foundation of China(31921004,31871533,and 31760300)+1 种基金the Laboratory of Lingnan Modern Agriculture Project(NT2021002)the Guangdong Basic and Applied Basic Research Foundation(2019A1515010230).
文摘Plant height is an important agronomic trait for lodging resistance and yield.Here,we report a new plantheight-related gene,OsUBR7 in rice(Oryza sativa L.);knockout of OsUBR7 caused fewer cells in internodes,resulting in a semi-dwarf phenotype.OsUBR7 encodes a putative E3 ligase containing a plant homeodomain finger and a ubiquitin protein ligase E3 component N-recognin 7(UBR7)domain.OsUBR7 interacts with histones and monoubiquitinates H2B(H2Bub1)at lysine148 in coordination with the E2 conjugase OsUBC18.OsUBR7 mediates H2Bub1 at a number of chromatin loci for the normal expression of target genes,including cell-cycle-related and pleiotropic genes,consistent with the observation that cell-cycle progression was suppressed in the osubr7 mutant owing to reductions in H2Bub1 and expression levels at these loci.The genetic divergence of OsUBR7 alleles among japonica and indica cultivars affects their transcriptional activity,and these alleles may have undergone selection during rice domestication.Overall,our results reveal a novel mechanism that mediates H2Bub1 in plants,and UBR7 orthologs could be utilized as an untapped epigenetic resource for crop improvement.
