The growing interest in post-translational protein modification,particularly in SU-MOylation,is driven by its crucial role in cell cycle regulation.SUMOylation affects various cell cycle regulators,including oncogenes...The growing interest in post-translational protein modification,particularly in SU-MOylation,is driven by its crucial role in cell cycle regulation.SUMOylation affects various cell cycle regulators,including oncogenes,suggesting its relevance in cancer.SUMO E3 ligases are pivotal in this process,exhibiting diverse functionalities through structural domains and sub-cellular localizations.A less-explored SUMO E3 ligase,RANBP2,a component of the vertebrate nuclear pore complex,emerges as a central player in cellular cycle processes,as well as in tumorigenesis.The current studies illuminate the importance of RANBP2 and underscore the need for more extensive studies to validate its clinical applicability in neoplastic interventions.Our review elucidates the significance of RANBP2 across various types of malignancies.Addi-tionally,it delves into exploring RANBP2 as a prospective therapeutic target for cancer treat-ment,offering insights into the avenues that scholars should pursue in their subsequent research endeavors.Thus,further investigation into RANBP2’s role in solid tumorigenesis is eagerly awaited.展开更多
Introduction:Acute necrotizing encephalopathy(ANE),a fatal subtype of infection-triggered encephalopathy syndrome(ITES),can be triggered by many systemic infections.RANBP2 gene mutations were associated with recurrent...Introduction:Acute necrotizing encephalopathy(ANE),a fatal subtype of infection-triggered encephalopathy syndrome(ITES),can be triggered by many systemic infections.RANBP2 gene mutations were associated with recurrent ANE.Case presentation:Here we report a 1-year-old girl with recurrent ITES and RANBP2 mutation.She was diagnosed with influenza-associated encephalopathy and made a full recovery on the first episode.After severe acute respiratory syndrome coronavirus 2 infection,the patient presented with seizures and deteriorating mental status.Brain magnetic resonance imaging revealed necrotic lesions in bilateral thalami and pons.Methylprednisolone,immunoglobulin,and interleukin 6 inhibitors were administered.Her consciousness level was improved at discharge.Nineteen cases of 2019 coronavirus disease-related ANE have been reported,of which 22.2%of patients died and 61.1%had neurologic disabilities.RANBP2 gene mutation was found in five patients,two of whom developed recurrent ITES.Conclusion:Patients with RANBP2 mutations are at risk for recurrent ITES,may develop ANE,and have a poor prognosis after relapse.展开更多
Alpha-fetoprotein (AFP) is the most widely used biomarker for the diagnosis of hepatocellular carcinoma (HCC). However, asubstantial proportion of HCC patients have either normal or marginally increased AFP levels in ...Alpha-fetoprotein (AFP) is the most widely used biomarker for the diagnosis of hepatocellular carcinoma (HCC). However, asubstantial proportion of HCC patients have either normal or marginally increased AFP levels in serum, and the underlyingmechanisms are not fully understood. In the present study, we provided in vitro and in vivo evidence that heat shock protein gp96promoted AFP expression at the transcriptional level in HCC. NR5A2 was identified as a key transcription factor for the AFP gene, andits stability was enhanced by gp96. A further mechanistic study by co-immunoprecipitation, GST pull-down, and molecular dockingshowed gp96 and the SUMO E3 ligase RanBP2 competitively binding to NR5A2 at the sites spanning from aa 507 to aa 539. Thebinding of gp96 inhibited SUMOylation, ubiquitination, and subsequent degradation of NR5A2. In addition, clinical analysis of HCCpatients indicated that gp96 expression in tumors was positively correlated with serum AFP levels. Therefore, our study uncovered anovel mechanism that gp96 regulates the stability of its client proteins by directly affecting their SUMOylation and ubiquitination.These findings will help in designing more accurate AFP-based HCC diagnosis and progression monitoring approaches.展开更多
基金supported by the National Natural Science Foundation of China(No.82273457)the Guangdong Basic and Applied Basic Research Foundation of China(No.2023A1515012762 and 2021A1515010846)+2 种基金Special Grant for Key Area Programs of Guangdong Education Department(China)(No.2021ZDZX2040)Science and Technology Special Project of Guangdong Province,China(No.210715216902829)“Dengfeng Project”for the construction of high-level hospitals in Guangdong Provinced First Affiliated Hospital of Shantou University College Supporting Funding(No.202003-10).
文摘The growing interest in post-translational protein modification,particularly in SU-MOylation,is driven by its crucial role in cell cycle regulation.SUMOylation affects various cell cycle regulators,including oncogenes,suggesting its relevance in cancer.SUMO E3 ligases are pivotal in this process,exhibiting diverse functionalities through structural domains and sub-cellular localizations.A less-explored SUMO E3 ligase,RANBP2,a component of the vertebrate nuclear pore complex,emerges as a central player in cellular cycle processes,as well as in tumorigenesis.The current studies illuminate the importance of RANBP2 and underscore the need for more extensive studies to validate its clinical applicability in neoplastic interventions.Our review elucidates the significance of RANBP2 across various types of malignancies.Addi-tionally,it delves into exploring RANBP2 as a prospective therapeutic target for cancer treat-ment,offering insights into the avenues that scholars should pursue in their subsequent research endeavors.Thus,further investigation into RANBP2’s role in solid tumorigenesis is eagerly awaited.
文摘Introduction:Acute necrotizing encephalopathy(ANE),a fatal subtype of infection-triggered encephalopathy syndrome(ITES),can be triggered by many systemic infections.RANBP2 gene mutations were associated with recurrent ANE.Case presentation:Here we report a 1-year-old girl with recurrent ITES and RANBP2 mutation.She was diagnosed with influenza-associated encephalopathy and made a full recovery on the first episode.After severe acute respiratory syndrome coronavirus 2 infection,the patient presented with seizures and deteriorating mental status.Brain magnetic resonance imaging revealed necrotic lesions in bilateral thalami and pons.Methylprednisolone,immunoglobulin,and interleukin 6 inhibitors were administered.Her consciousness level was improved at discharge.Nineteen cases of 2019 coronavirus disease-related ANE have been reported,of which 22.2%of patients died and 61.1%had neurologic disabilities.RANBP2 gene mutation was found in five patients,two of whom developed recurrent ITES.Conclusion:Patients with RANBP2 mutations are at risk for recurrent ITES,may develop ANE,and have a poor prognosis after relapse.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29040000)the Industrial Innovation Team grant from Foshan Industrial Technology Research Institute,Chinese Academy of Sciences,the National Natural Science Foundation of China(32070163,81871297,and 81903142)China ATOMIC Energy Authority,Foshan High-level Hospital Construction DengFeng Plan,and Guangdong Province Biomedical Innovation Platform Construction Project Tumor Immunobiotherapy.
文摘Alpha-fetoprotein (AFP) is the most widely used biomarker for the diagnosis of hepatocellular carcinoma (HCC). However, asubstantial proportion of HCC patients have either normal or marginally increased AFP levels in serum, and the underlyingmechanisms are not fully understood. In the present study, we provided in vitro and in vivo evidence that heat shock protein gp96promoted AFP expression at the transcriptional level in HCC. NR5A2 was identified as a key transcription factor for the AFP gene, andits stability was enhanced by gp96. A further mechanistic study by co-immunoprecipitation, GST pull-down, and molecular dockingshowed gp96 and the SUMO E3 ligase RanBP2 competitively binding to NR5A2 at the sites spanning from aa 507 to aa 539. Thebinding of gp96 inhibited SUMOylation, ubiquitination, and subsequent degradation of NR5A2. In addition, clinical analysis of HCCpatients indicated that gp96 expression in tumors was positively correlated with serum AFP levels. Therefore, our study uncovered anovel mechanism that gp96 regulates the stability of its client proteins by directly affecting their SUMOylation and ubiquitination.These findings will help in designing more accurate AFP-based HCC diagnosis and progression monitoring approaches.
