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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Main Authors: Jian Sun, Cui Liu, Changhui Lang, Jing Wang, Qingxiang Li, Chang Peng, Zuochen Du, Yan Chen, Pei Huang
Format: Article
Language:English
Published: Elsevier 2025-05-01
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.
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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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