AIM To investigate the function and mechanism of ubiquitinlike modifier activating enzyme 2(Uba2) in progression of gastric cancer(GC) cells.METHODS Uba2 level in patients with GC was analyzed by Western blotting and ...AIM To investigate the function and mechanism of ubiquitinlike modifier activating enzyme 2(Uba2) in progression of gastric cancer(GC) cells.METHODS Uba2 level in patients with GC was analyzed by Western blotting and immunohistochemistry. MTT and colony formation assays were performed to examine cell proliferation.Flow cytometry was used for cell cycle analysis.Wound healing and Transwell assays were conducted to examine the effects of Uba2 on migration and invasion.Expression levels of cell cycle-related proteins, epithelial-mesenchymal transition(EMT) biomarkers, and involvement of the Wnt/β-catenin pathway was assessed by Western blotting. Activation of the Wnt/β-catenin pathway was confirmed by luciferase assay.RESULTS Uba2 expression was higher in GC than in normal tissues.Increased Uba2 expression was correlated with tissue differentiation, Lauren's classification, vascular invasion,and TNM stage, as determined by the analysis of 100 GC cases(P < 0.05). Knock-down of Uba2 inhibited GC cell proliferation, induced cell cycle arrest, and altered expression of cyclin D1, P21, P27, and Bcl-2, while upregulation of Uba2 showed the opposite effects. The wound healing and Transwell assays showed that Uba2 promoted GC cell migration and invasion. Western blotting revealed alterations in EMT biomarkers, suggesting the role of Uba2 in EMT. Furthermore, the luciferase reporter assay indicated the involvement of the Wnt/β-catenin signaling pathway as a possible modulator of Uba2 oncogenic functions.CONCLUSION Uba2 plays a vital role in GC cell migration and invasion,possibly by regulating the Wnt/β-catenin signaling pathway and EMT.展开更多
Small ubiquitin-like modifier(SUMO)-conjugating enzymes are involved in post-translational regulatory processes in eukaryotes, including the conjugation of SUMO peptides to protein substrate(SUMOylation). SUMOylation ...Small ubiquitin-like modifier(SUMO)-conjugating enzymes are involved in post-translational regulatory processes in eukaryotes, including the conjugation of SUMO peptides to protein substrate(SUMOylation). SUMOylation plays an important role in improving plant tolerance to abiotic stress such as salt, drought, heat and cold. Herein, we reported the isolation of OsSCE1(LOC_Os10 g39120) gene encoding a SUMO-conjugating enzyme from rice(Oryza sativa cv. Nipponbare) and its functional validation in response to drought stress. The E2 enzyme, Os SCE1, is one of three key enzymes involved in the conjugation of SUMO to its target proteins. Activated SUMO is transferred to the cysteine of an E2 enzyme and then to the target lysine residue of the substrate, with or without the help of an E3 SUMO ligase. Expression of OsSCE1 was strongly induced by polyethylene glycol 6000(PEG6000) treatment, which suggested OsSCE1 may be involved in the drought stress response. Overexpression of OsSCE1(OsSCE1-OX) in Nipponbare reduced the tolerance to drought stress. Conversely, the drought tolerance was slightly improved by the knockdown of OsSCE1(OsSCE1-KD). These results were further supported by measurement of proline content in OsSCE1-OX and OsSCE1-KD transgenic lines under induced drought stress, which showed OsSCE1-KD transgenic lines accumulated higher proline content than the wild type, whereas OsSCE1-OX line had lower proline content than the wild type. These findings suggested OsSCE1 may play a role as a negative regulator in response to drought stress in rice.展开更多
Histone modifications are key factors in chromatin packaging,and are responsible for gene regulation during cell fate determination and development.Abnormal alterations in histone modifications potentially affect the ...Histone modifications are key factors in chromatin packaging,and are responsible for gene regulation during cell fate determination and development.Abnormal alterations in histone modifications potentially affect the stability of the genome and disrupt gene expression patterns,leading to many diseases,including cancer.In recent years,mounting evidence has shown that various histone modifications altered by aberrantly expressed modifier enzymes contribute to tumor development and metastasis through the induction of epigenetic,transcriptional,and phenotypic changes.In this review,we will discuss the existing histone modifications,both well-studied and rare ones,and their roles in solid tumors and hematopoietic cancers,to identify the molecular pathways involved and investigate targeted therapeutic drugs to reorganize the chromatin and enhance cancer treatment efficiency.Finally,clinical inhibitors of histone modifications are summarized to better understand the developmental stage of cancer therapy in using these drugs to inhibit the histone modification enzymes.展开更多
Small ubiquitin-like modifier （SUMO） conjugation affects a broad range of processes in plants, including growth, flower initiation, pathogen defense, and responses to abiotic stress. Here, we investigate in vivo and...Small ubiquitin-like modifier （SUMO） conjugation affects a broad range of processes in plants, including growth, flower initiation, pathogen defense, and responses to abiotic stress. Here, we investigate in vivo and in vitro a SUMO conjugating enzyme with a Cys to Ser change in the active site, and show that it has a dominant negative effect. In planta expression significantly perturbs normal development, leading to growth retardation, early flowering and gene expression changes. We suggest that the mutant protein can serve as a probe to investigate sumoylation, also in plants for which poor genetic infrastructure precludes analysis via loss-of-function mutants.展开更多
基金the Science and Technology Department of Jilin Province(No.20150204006YY)
文摘AIM To investigate the function and mechanism of ubiquitinlike modifier activating enzyme 2(Uba2) in progression of gastric cancer(GC) cells.METHODS Uba2 level in patients with GC was analyzed by Western blotting and immunohistochemistry. MTT and colony formation assays were performed to examine cell proliferation.Flow cytometry was used for cell cycle analysis.Wound healing and Transwell assays were conducted to examine the effects of Uba2 on migration and invasion.Expression levels of cell cycle-related proteins, epithelial-mesenchymal transition(EMT) biomarkers, and involvement of the Wnt/β-catenin pathway was assessed by Western blotting. Activation of the Wnt/β-catenin pathway was confirmed by luciferase assay.RESULTS Uba2 expression was higher in GC than in normal tissues.Increased Uba2 expression was correlated with tissue differentiation, Lauren's classification, vascular invasion,and TNM stage, as determined by the analysis of 100 GC cases(P < 0.05). Knock-down of Uba2 inhibited GC cell proliferation, induced cell cycle arrest, and altered expression of cyclin D1, P21, P27, and Bcl-2, while upregulation of Uba2 showed the opposite effects. The wound healing and Transwell assays showed that Uba2 promoted GC cell migration and invasion. Western blotting revealed alterations in EMT biomarkers, suggesting the role of Uba2 in EMT. Furthermore, the luciferase reporter assay indicated the involvement of the Wnt/β-catenin signaling pathway as a possible modulator of Uba2 oncogenic functions.CONCLUSION Uba2 plays a vital role in GC cell migration and invasion,possibly by regulating the Wnt/β-catenin signaling pathway and EMT.
基金supported by Unggulan Research Grant from the Indonesian Institute of Sciences(LIPI)(Grant No.1139/F/2015)
文摘Small ubiquitin-like modifier(SUMO)-conjugating enzymes are involved in post-translational regulatory processes in eukaryotes, including the conjugation of SUMO peptides to protein substrate(SUMOylation). SUMOylation plays an important role in improving plant tolerance to abiotic stress such as salt, drought, heat and cold. Herein, we reported the isolation of OsSCE1(LOC_Os10 g39120) gene encoding a SUMO-conjugating enzyme from rice(Oryza sativa cv. Nipponbare) and its functional validation in response to drought stress. The E2 enzyme, Os SCE1, is one of three key enzymes involved in the conjugation of SUMO to its target proteins. Activated SUMO is transferred to the cysteine of an E2 enzyme and then to the target lysine residue of the substrate, with or without the help of an E3 SUMO ligase. Expression of OsSCE1 was strongly induced by polyethylene glycol 6000(PEG6000) treatment, which suggested OsSCE1 may be involved in the drought stress response. Overexpression of OsSCE1(OsSCE1-OX) in Nipponbare reduced the tolerance to drought stress. Conversely, the drought tolerance was slightly improved by the knockdown of OsSCE1(OsSCE1-KD). These results were further supported by measurement of proline content in OsSCE1-OX and OsSCE1-KD transgenic lines under induced drought stress, which showed OsSCE1-KD transgenic lines accumulated higher proline content than the wild type, whereas OsSCE1-OX line had lower proline content than the wild type. These findings suggested OsSCE1 may play a role as a negative regulator in response to drought stress in rice.
基金supported by grants from National Natural Science Foundation of China(grant number:42125707,41931291)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(grant number:2019PT310027)+1 种基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(grant number:2021-RC310-006,2021-I2M-1-018,2021-RC310-018,2020-RC310-008)China Postdoc-toral Science Foundation(grant number:2022M710454).
文摘Histone modifications are key factors in chromatin packaging,and are responsible for gene regulation during cell fate determination and development.Abnormal alterations in histone modifications potentially affect the stability of the genome and disrupt gene expression patterns,leading to many diseases,including cancer.In recent years,mounting evidence has shown that various histone modifications altered by aberrantly expressed modifier enzymes contribute to tumor development and metastasis through the induction of epigenetic,transcriptional,and phenotypic changes.In this review,we will discuss the existing histone modifications,both well-studied and rare ones,and their roles in solid tumors and hematopoietic cancers,to identify the molecular pathways involved and investigate targeted therapeutic drugs to reorganize the chromatin and enhance cancer treatment efficiency.Finally,clinical inhibitors of histone modifications are summarized to better understand the developmental stage of cancer therapy in using these drugs to inhibit the histone modification enzymes.
基金supported by the Max Planck Societythe German Research Foundation DFG (SFB 635 to G.C., and SPP 1365 and grant BA1158/3–1 to A.B.)+1 种基金the Austrian Research Foundation FWF (grant P 21215 to A.B.)pre-doctoral fellowships from the International Max Planck Research School to R.B. and R.H
文摘Small ubiquitin-like modifier （SUMO） conjugation affects a broad range of processes in plants, including growth, flower initiation, pathogen defense, and responses to abiotic stress. Here, we investigate in vivo and in vitro a SUMO conjugating enzyme with a Cys to Ser change in the active site, and show that it has a dominant negative effect. In planta expression significantly perturbs normal development, leading to growth retardation, early flowering and gene expression changes. We suggest that the mutant protein can serve as a probe to investigate sumoylation, also in plants for which poor genetic infrastructure precludes analysis via loss-of-function mutants.
