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
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2026
·
IF 12.2
Zhang Zhe,Xiao Bing,Jiang Yupeng,Niu Lixia,Wang Li,Cai Juan
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide, and understanding its molecular drivers is critical for improving therapeutic outcomes. SUMOylation is a form of post-translational modification that conjugates small ubiquitin-like modifier (SUMO) to specific lysine residues of target proteins. The sole SUMO E2-conjugating enzyme UBC9 is upregulated in multiple malignancies, yet its functional role and specific substrate in LUAD remain poorly defined. Here, we demonstrate that UBC9 is significantly elevated in LUAD tissues, and its high expression is associated with adverse clinic outcomes. Functional assays revealed that genetic ablation of UBC9 robustly suppresses LUAD cell proliferation, migration, invasion, and tumorigenesis both in vitro and in vivo. Through immunoprecipitation-mass spectrometry, we identified Coronin-1C (CORO1C), a master regulator of actin dynamics, as a key substrate of UBC9-mediated SUMOylation. Mechanistically, SUMOylation of CORO1C at lysine residues K19, K311, and K440 enhances its binding to actin-related protein 2 (Arp2) complex, promotes actin‑based cytoskeletal remodeling, and drives malignant cellular behaviors. Collectively, our work reveals a previously unrecognized regulatory axis in which UBC9‑dependent SUMOylation licenses CORO1C to orchestrate Arp2/3‑mediated cytoskeletal dynamics, thereby advancing LUAD progression. These findings reveal CORO1C as a novel SUMOylation target in lung adenocarcinoma and offer new mechanistic insights into tumor cell motility, but also highlight a promising therapeutic avenue for treating advanced LUAD.
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产品关联
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
✓ 已验证
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）