Inhibiting neddylation: A new strategy for tumor therapy
Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme (NAE) (E1), E2 NEDD8-conjugating e...
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Elsevier
2025-05-01
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| Series: | Journal of Pharmaceutical Analysis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177924002375 |
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| author | Jian Sun Cui Liu Changhui Lang Jing Wang Qingxiang Li Chang Peng Zuochen Du Yan Chen Pei Huang |
| author_facet | Jian Sun Cui Liu Changhui Lang Jing Wang Qingxiang Li Chang Peng Zuochen Du Yan Chen Pei Huang |
| author_sort | Jian Sun |
| collection | DOAJ |
| description | Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme (NAE) (E1), E2 NEDD8-conjugating enzyme (E2), and E3 NEDD8-ligase (E3). The most extensively studied substrates of neddylation are members of the cullin family, which act as scaffold components for cullin ring E3 ubiquitin ligases (CRLs). Since cullin neddylation activates CRLs, which are frequently overactive in tumors, inhibiting neddylation has emerged as a promising strategy for developing novel antitumor therapies. This review explores the antitumor effects of inhibiting neddylation that leads to the inactivation of CRLs and provides a summary of known inhibitors that target protein-protein interactions (PPIs) within the neddylation enzymatic cascade. |
| format | Article |
| id | doaj-art-2be1c7929f6c47e9a5aa9dbaf6b164ff |
| institution | Kabale University |
| issn | 2095-1779 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj-art-2be1c7929f6c47e9a5aa9dbaf6b164ff2025-08-20T03:48:18ZengElsevierJournal of Pharmaceutical Analysis2095-17792025-05-0115510114010.1016/j.jpha.2024.101140Inhibiting neddylation: A new strategy for tumor therapyJian Sun0Cui Liu1Changhui Lang2Jing Wang3Qingxiang Li4Chang Peng5Zuochen Du6Yan Chen7Pei Huang8Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, China; Department of Pediatrics, Guizhou Children's Hospital, Zunyi, Guizhou, 563000, China; Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine, Zunyi Medical University, Zunyi, Guizhou, 563000, ChinaDepartment of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, China; Department of Pediatrics, Guizhou Children's Hospital, Zunyi, Guizhou, 563000, ChinaDepartment of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, China; Department of Pediatrics, Guizhou Children's Hospital, Zunyi, Guizhou, 563000, ChinaDepartment of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, China; Department of Pediatrics, Guizhou Children's Hospital, Zunyi, Guizhou, 563000, ChinaDepartment of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, China; Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine, Zunyi Medical University, Zunyi, Guizhou, 563000, ChinaDepartment of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, China; Department of Pediatrics, Guizhou Children's Hospital, Zunyi, Guizhou, 563000, ChinaDepartment of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, China; Corresponding author.Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, China; Department of Pediatrics, Guizhou Children's Hospital, Zunyi, Guizhou, 563000, China; Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine, Zunyi Medical University, Zunyi, Guizhou, 563000, China; Corresponding author. Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, China.Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, China; Department of Pediatrics, Guizhou Children's Hospital, Zunyi, Guizhou, 563000, China; Corresponding author. Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, China.Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme (NAE) (E1), E2 NEDD8-conjugating enzyme (E2), and E3 NEDD8-ligase (E3). The most extensively studied substrates of neddylation are members of the cullin family, which act as scaffold components for cullin ring E3 ubiquitin ligases (CRLs). Since cullin neddylation activates CRLs, which are frequently overactive in tumors, inhibiting neddylation has emerged as a promising strategy for developing novel antitumor therapies. This review explores the antitumor effects of inhibiting neddylation that leads to the inactivation of CRLs and provides a summary of known inhibitors that target protein-protein interactions (PPIs) within the neddylation enzymatic cascade.http://www.sciencedirect.com/science/article/pii/S2095177924002375NeddylationTumorAntitumorInhibitorPPI |
| spellingShingle | Jian Sun Cui Liu Changhui Lang Jing Wang Qingxiang Li Chang Peng Zuochen Du Yan Chen Pei Huang Inhibiting neddylation: A new strategy for tumor therapy Journal of Pharmaceutical Analysis Neddylation Tumor Antitumor Inhibitor PPI |
| title | Inhibiting neddylation: A new strategy for tumor therapy |
| title_full | Inhibiting neddylation: A new strategy for tumor therapy |
| title_fullStr | Inhibiting neddylation: A new strategy for tumor therapy |
| title_full_unstemmed | Inhibiting neddylation: A new strategy for tumor therapy |
| title_short | Inhibiting neddylation: A new strategy for tumor therapy |
| title_sort | inhibiting neddylation a new strategy for tumor therapy |
| topic | Neddylation Tumor Antitumor Inhibitor PPI |
| url | http://www.sciencedirect.com/science/article/pii/S2095177924002375 |
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