ONCOGENE
·
2025
·
IF 7.3
Wei Xiaosong,Wang Beibei,Yang Yang,Fang Zhiwei,Yi Chengzhi,Zhang Liuhui,Fan Xin,Tang Dongdong,Zhang Lirong,Yang Xiaoming,Song Dongkui
Zinc finger protein 24 (ZNF24) is a conserved multifunctional transcription factor associated with tumorigenesis, but its function in bladder carcinogenesis remains unclear. Herein, the expression of ZNF24 was decreased in bladder cancer (BC) cells and tissues, and patients with higher expression of ZNF24 had a better prognosis. Doxycycline-induced overexpression and knockdown of ZNF24 identified its anti-proliferative and anti-metastasis role in BC in vitro and in vivo. The potential genes for the anti-cancer role of ZNF24, involving transcriptional regulation of several factors, such as dual-specificity phosphatase 1 and squalene epoxidase. E2 conjugating enzyme UBC9 and small ubiquitin-like modifier (SUMO) 1 were found to interact with ZNF24, suggesting that ZNF24 may be SUMOylated. Consistent with the expression, ZNF24 SUMOylation levels were decreased in BC cells and tissues. Pan-SUMOylation inhibition promoted protein degradation of ZNF24. UBC9 SUMOylated ZNF24 at Lys-27 (K27) site with SUMO1 modification and the K27 mutation of ZNF24 greatly damaged the protein stability of ZNF24. Cullin 3 (CUL3), a E3 ubiquitin ligase, was responsible for the degradation of ZNF24. ZNF24 SUMOylation prevented CUL3-mediated protein degradation of ZNF24. Overall, the crosstalk between the SUMOylation and ubiquitination of ZNF24 may be a novel regulatory mechanism to block tumorigenesis and development of BC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Sibo Wang,Jingsong Guo,Yanyan Peng,Jing Han,Zhaowen Jiang,Xiaoxue Hu,Shaoqing Gao,Xiaoxia Wu,Wei Ji
The 26S proteasome is a crucial protease complex responsible for degrading specific proteins to maintain cellular function during salt stress. Previous studies have shown that GmRPN11d, a subunit of the regulatory particle in soybean, is upregulated in response to short-term salt stress. This research discovered that GmRPN11d is localized in the nucleus and cytoplasm, with its expression increasing under high salinity and other stress conditions. Overexpressing GmRPN11d in Arabidopsis and soybean hairy roots significantly improves salt stress tolerance. Examination of physiological indices and expression patterns of salt-responsive marker genes reveals that overexpression of GmRPN11d enhances the ability to scavenge reactive oxygen species, regulates ion balance, exhibits hypersensitivity to ABA, and activates the ABA signaling pathway under salt stress. Additionally, GmRPN11d was demonstrated to interact with the SUMO E3 ligase GmMMS21 in both in vivo and in vitro experiments. This interaction serves to facilitate the SUMOylation of GmRPN11d, ultimately contributing to its stability when faced with salt stress. Taken together, these findings highlight the role of GmRPN11d in promoting plant salt tolerance through SUMOylation, mediated by GmMMS21. This study provides valuable insights into modifying the 26S proteasome subunit in soybean, offering a potential target gene for developing genetically modified salt-resistant crops.
研究领域:
植物学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Sibo Wang,Zhaowen Jiang,Ruixue Chen,Jingbin Duan,Jingsong Guo,Jianing Li,Liang Yang,Xiaoxia Wu,Wei Ji
The translationally controlled tumor protein (TCTP) represents a multifunctional and evolutionarily conserved protein family in eukaryotes. Despite its biological significance, the genetic characteristics and stress-responsive mechanisms of TCTP remain uncharacterized in soybean. This study identifies GmTCTP2 as a drought-responsive gene showing transcriptional upregulation under PEG-induced dehydration and multiple abiotic stresses. Through comprehensive interaction assays including GST pull-down, co-immunoprecipitation (Co-IP), and bimolecular fluorescence complementation (BiFC), we demonstrate that GmTCTP2 physically interacts with the SUMO E2 conjugate enzyme GmSCEc. This interaction enables GmTCTP2 SUMOylation at lysine residues 101 and 167, significantly enhancing its protein stability under drought conditions. Phenotypic analysis revealed that the Arabidopsis TCTP mutant Attctp displays drought-sensitive characteristics, which could be fully complemented by wild-type GmTCTP2 but not by its SUMOylation-deficient variant GmTCTP2 K101 , 167R . Transgenic Arabidopsis overexpressing GmTCTP2 exhibited substantially improved drought tolerance through enhanced photosynthetic efficiency, ROS scavenging capacity, and hormonal signaling modulation, as evidenced by physiological assessments and transcriptomic profiling. Our findings establish that GmSCEc-mediated SUMOylation of GmTCTP2 critically contributes to drought stress adaptation, providing both mechanistic insights into TCTP regulation and valuable genetic resources for engineering drought-resistant crops.
研究领域:
植物学
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分子遗传学
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DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2023
·Vol. 27
·期 2
·1-10
·
IF 3.4
Cunyang Gu,Feng Gao,Shiqi Zhang,Lihua Kang,Wei Zhang,Xiaojuan Feng,Jinxi Liu,Yuexin Tian,Qun Wei,Yunxia Du,Yujia Xing,Qingjuan Liu,Shuxia Liu
Tubulointerstitial fibrosis (TIF) is an important pathological change that occurs during the development of diabetic kidney disease. The epithelial‑mesenchymal transition (EMT) of renal tubular epithelial cells is a manifestation of TIF. STAT1, a member of the STAT family of transcription factors, can be modified by the small ubiquitin‑related modifier (SUMO), thus affecting the activity of STAT1. The present study investigated the role of STAT1 SUMOylation in high glucose‑induced tubular EMT by western blotting, immunocytochemistry, immunofluorescence, co‑immunoprecipitation and dual luciferase reporter analysis. The results indicated that in the process of high glucose‑induced EMT, STAT1 activation protected the cells from EMT. However, high glucose also increased the SUMOylation of STAT1, which prevented STAT1 from exerting an effective protective role by inhibiting its activity.
研究领域:
分子生物学
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细胞生物学
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糖尿病研究
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肾病学
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DOI
PubMed
高影响因子
AUTOIMMUNITY
·
2020
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IF 2.125
Cao Yongjun,Qiao Nan,Sun Yumeng,Jin Xiaowen,Wen Weibo
Dioscin has been used as a treatment for Hashimoto’s thyroiditis (HT) in China. However, the molecular mechanisms governing the modes of action of dioscin have not been elucidated. In this study, flow cytometry and Western blotting were used to identify the proportions of CD4+CD25+ regulatory T (Treg) cells and the expression of forkhead box P3 (Foxp3) and SUMO-specific protease 1 (SENP1) in HT patients’ peripheral blood mononuclear cells (PBMCs). A pTg-induced rat model of HT was established by injection of 100 μg pTg. Then, the model rats were randomly divided into three groups (n = 5): control (NC), model (HT) and dioscin treatment. After oral administration of dioscin each day for two weeks, CD4+CD25+Foxp3+ Treg cells were analysed by flow cytometry, and the protein expression levels of SENP1, Foxp3, SUMO-1 and SUMO-2/3 were measured by Western blotting. Co-immunoprecipitation (Co-IP) was used to identify the SUMOylation of interferon regulatory factor 4 (IRF4). The results showed that the proportions of CD4+CD25+ Treg cells and the expression of Foxp3 were significantly decreased in HT patients, but the expression of SENP1 was enhanced compared to healthy controls (HCs). However, compared to the pTg-induced HT rat group, the expression of Foxp3, SUMO-1, and SUMO-2/3 and the proportions of CD4+CD25+Foxp3+ Treg cells were increased, whereas the expression of SENP1 was decreased, in the dioscin-treated group. Furthermore, the SUMOylation of IRF4 was increased after SENP1 was knocked down. The results of our study indicate that dioscin can promote the differentiation of the CD4+CD25+Foxp3+ Treg cells and subsequently upregulate the SUMOylation of IRF4 by downregulating SENP1 expression.
研究领域:
免疫学
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分子生物学
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内分泌学
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DOI
PubMed
高影响因子
Postepy Dermatologii i Alergologii
·
2025
·Vol. 42
·期 4
·398-406
·
IF 1.7
Bei Zhao,Yinghua Liu,Xuemei Tang,Shi Cheng
Introduction:The effectiveness of chemotherapy in treating melanoma is limited due to drug resistance. Previous studies have shown that SENP1 (Sentrin/SUMO-specific protease 1) is related to the tumour hypoxic microenvironment, tumorigenesis and metastasis.Aim:This study aimed to investigate its roles in drug resistance of melanoma.Material and methods:Originally, a concentration of 2 µg/ml dacarbazine (DTIC) was employed in the treatment of A375 and M14 cell lines for a duration of 24 h. Subsequently, the cells were transferred to fresh medium and allowed to proliferate until reaching 80% of their maximum density. This treatment cycle was then repeated for a total of 10 days, following which the DTIC concentration was doubled. The establishment of drug-resistant cell lines for both A375 and M14 occurred after 8 months of sustained and continuous treatment. The expression level of SENP1 was monitored monthly using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), with a fold change above 1.5 compared to the untreated condition considered as significant.Results:Finally, the study found that SENP1 was up-regulated by about 2.2-1.7 times in the drug-resistant cells. In addition, overexpression of SENP1 in normal A375 cells improved cell viability against DTIC. The study also found that Yes-associated protein (YAP) could form protein condensates in the cytoplasm while its expression was enhanced by SENP1-mediated deSUMOylation.Conclusions:This study suggests that there is a positive correlation between the ubiquitin-specific protease SENP1 and drug resistance in melanoma. Its up-regulation may lead to changes in the deSUMOylation of YAP, activate the Hippo signalling pathway, and increase the resistance of melanoma to DTIC.
研究领域:
癌症生物学
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分子生物学
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药理学
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细胞生物学
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生物化学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Se-Ruo Li,Ning-Ning Kang,Rong-Rong Wang,Meng-Die Li,Li-Hong Chen,Peng Zhou,De-Xiang Xu,Hui Zhao,Lin Fu
Our previous study revealed that 1-nitropyrene (1-NP) exposure evoked pulmonary fibrosis in mice. However, the exact mechanism remained elusive. We found that 1-NP induced telomere damage and cellular senescence in mice lungs, and two alveolar epithelial cells lines. 1-NP downregulated telomere repeat binding factor 2 (TRF2), and upregulated FBXW7. Mechanistically, 1-NP-caused TRF2 ubiquitination and proteasomal degradation depended on E3 ubiquitin ligase activity of FBXW7. Moreover, 1-NP upregulated FBXW7 m6A modification via an ALKBH5-YTHDF1-dependent manner. Further analysis suggested 1-NP promoted ALKBH5 SUMOylation and subsequent proteasomal degradation. Additionally, 1-NP evoked mitochondrial reactive oxygen species (mtROS) overproduction. Mito-TEMPO, a mitochondrial-targeted antioxidant, mitigated 1-NP-caused mtROS overproduction, ALKBH5 SUMOylation, FBXW7 m6A modification, TRF2 degradation, cellular senescence, and pulmonary fibrosis. Taken together, mtROS-initiated ALKBH5 SUMOylation and subsequent FBXW7 m6A modification is indispensable for TRF2 degradation and cellular senescence in alveolar epithelial cells during 1-NP-induced pulmonary fibrosis. Our study provides target intervention measures towards 1-NP-evoked pulmonary fibrosis. Environmental Implication 1-nitropyrene (1-NP) is a representative of nitro polycyclic aromatic hydrocarbon compound that can be formed during the insufficient combustion of organic substances like coal, oil, gas, and tobacco. Moreover, mounting researches have revealed that 1-NP can cause various respiratory system diseases, inclusive of acute lung injury, chronic obstructive pulmonary disease, and allergic asthma. The current research provides evidence that exposure to 1-NP induces pulmonary fibrosis through evoking telomere damage and cellular senescenc. What’s more, Mito-TEMPO, a mitochondrial-targeted antioxidant, can mitigate 1-NP-caused cellular senescence and pulmonary fibrosis. Our study provides target intervention measures towards 1-NP-evoked pulmonary fibrosis.
研究领域:
毒理学
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肺科学
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细胞生物学
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分子生物学
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环境健康
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DOI
PubMed
高影响因子
EXPERIMENTAL EYE RESEARCH
·
2022
·
IF 3.77
Min Chen,Qianhui Zhang,Shun Wang,Feng Zheng
Retinal microvascular endothelial cell (RMEC) injury plays an important role in the pathophysiology diabetic retinopathy (DR). The GTPase dynamin-related protein 1 (Drp1), crucial to mitochondrial dynamics , has been implicated in hyperglycaemia-induced microvascular damage. Moreover, Drp1 can be deSUMOylated by the enzyme sentrin/SUMO-specific protease 3 (SENP3). Whether SENP3/deSUMOylated Drp1 can aggravate DR is unclear. Therefore, we designed this experiment to investigate the role of SENP3/desumoylated Drp1 in DR in vitro and in vivo. Murine RMECs (mRMECs) were classified into a control (CON), high-glucose (HG) and high-glucose + SENP3-siRNA (HG-siRNA) groups. The SENP3 and SUMOylated/deSUMOylated drp1 levels, mitochondrial morphology, mitochondrial membrane potential (MMP) and apoptosis rate were evaluated. In vivo, mice were assigned to a normal, type 2 diabetic or type 2 diabetic SENP3-siRNA mouse groups. Then, blood–retinal barrier function and retinal tissue structure were evaluated. As compared to those in the control group, the SENP3 and Drp1 levels, degree of mitochondrial fragmentation, extent of MMP loss and apoptosis rate of mRMECs were significantly increased in the HG group. However, inhibited SENP3 expression increased the level of SUMOylated Drp1 in the mRMECs and reduced the hyperglycaemia-induced mitochondrial damage and apoptosis rate. These experimental results were confirmed by diabetic animal experiments showing that inhibited SENP3 expression attenuated the increase in retinal permeability and diabetic retinopathy, suggesting that SENP3/deSUMOylated Drp1 activation aggravated DR by disrupting mitochondrial dynamics and apoptosis. Furthermore, blocking SENP3 expression significantly attenuated RMEC damage and DR.
研究领域:
糖尿病
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分子生物学
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细胞生物学
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眼科学
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病理生理学
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DOI
PubMed
高影响因子
Journal of Fungi
·
2023
·Vol. 9
·期 1
·94
·
IF 4.7
Azizullah,Muhammad Noman,Yizhou Gao,Hui Wang,Xiaohui Xiong,Jiajing Wang,Dayong Li,Fengming Song
SUMOylation is an essential protein modification process that regulates numerous crucial cellular and biochemical processes in phytopathogenic fungi, and thus plays important roles in multiple biological functions. The present study characterizes the SUMOylation pathway components, including SMT3 (SUMO), AOS1 (an E1 enzyme), UBC9 (an E2 enzyme), and MMS21 (an E3 ligase), inFusarium oxysporumf. sp.niveum(Fon), the causative agent of watermelon Fusarium wilt, in terms of the phylogenetic relationship, gene/protein structures, and basic biological functions. The SUMOylation components FonSMT3, FonAOS1, FonUBC9, and FonMMS21 are predominantly located in the nucleus.FonSMT3,FonAOS1,FonUBC9, andFonMMS21are highly expressed in the germinating macroconidia, but their expression is downregulated gradually in infected watermelon roots with the disease progression. The disruption ofFonUBA2andFonSIZ1seems to be lethal inFon. The deletion mutant strains forFonSMT3,FonAOS1,FonUBC9, andFonMMS21are viable, but exhibit significant defects in vegetative growth, asexual reproduction, conidial morphology, spore germination, responses to metal ions and DNA-damaging agents, and apoptosis. The disruption ofFonSMT3,FonAOS1,FonUBC9, andFonMMS21enhances sensitivity to cell wall-perturbing agents, but confers tolerance to digestion by cell wall-degrading enzymes. Furthermore, the disruption ofFonSMT3,FonAOS1, andFonUBC9negatively regulates autophagy inFon. Overall, these results demonstrate that the SUMOylation pathway plays vital roles in regulating multiple basic biological processes inFon, and, thus, can serve as a potential target for developing a disease management approach to control Fusarium wilt in watermelon.Keywords:asexual reproduction;cell death;cell wall integrity;Fusarium oxysporumf. sp.niveum;mycelial growth;stress response;SUMOylation pathway;watermelon
研究领域:
植物病理学
·
分子生物学
·
真菌遗传学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）