NEDD8

Last update 08 May 2025

Basic Info

Synonyms

Nedd-8, NEDD8, NEDD8 ubiquitin like modifier

+ [3]

Introduction

Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis via its conjugation to a limited number of cellular proteins, such as cullins or p53/TP53 (PubMed:10318914, PubMed:10597293, PubMed:11953428, PubMed:14690597, PubMed:15242646, PubMed:9694792, PubMed:38605244). Attachment of NEDD8 to cullins is critical for the recruitment of E2 to the cullin-RING-based E3 ubiquitin-protein ligase complex, thus facilitating polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins (PubMed:10318914, PubMed:10597293, PubMed:11953428, PubMed:20688984, PubMed:9694792, PubMed:38605244). Attachment of NEDD8 to p53/TP53 inhibits p53/TP53 transcriptional activity (PubMed:15242646). Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M (PubMed:14690597).

100 Clinical Results associated with NEDD8

100 Translational Medicine associated with NEDD8

0 Patents (Medical) associated with NEDD8

904

Literatures (Medical) associated with NEDD8

31 Dec 2025·Hematology

Targeting NEDD8 in pediatric acute myeloid leukemia: an integrated bioinformatics and experimental approach

Article

Author: Liu, Cui ; Chen, Yan ; Zhu, Yin ; Sun, Jian ; Yang, Guangli ; Peng, Chang ; Zhang, Pingping ; Huang, Pei ; Du, Zuochen ; An, Yang ; Guan, Yaning ; Li, Qian

SUMMARYThis study systematically explored the role of NEDD8 in pediatric acute myeloid leukemia (AML) through patient sample analysis, database mining, and in vitro experiments. Our results demonstrated that NEDD8 was significantly overexpressed in newly diagnosed pediatric AML patients and was associated with poor survival outcomes. Functional enrichment analysis of the TARGET database further revealed a strong correlation between NEDD8 and cancer-related pathways. In vitro experiments showed that NEDD8 knockdown significantly inhibited the proliferation of AML cells (THP-1 and MV4-11) and induced cell cycle arrest. Collectively, these findings highlight the critical role of NEDD8 in pediatric AML pathogenesis and suggest its potential as both a prognostic biomarker and a therapeutic target.

01 Dec 2025·Cancer Chemotherapy and Pharmacology

A phase I study of MLN4924 and belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome

Article

Author: Piekarz, Richard ; Maher, Keri R ; Rudek, Michelle A ; Bandyopadhyay, Dipankar ; Harvey, R Donald ; Shafer, Danielle ; Schaar, Dale ; Wright, John ; Deng, Xiaoyan ; Grant, Steven

AbstractPurposeRelapsed and/or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome continue to have a poor prognosis with limited treatment options despite advancements in rational combination and targeted therapies. Belinostat (an HDAC inhibitor) and Pevonedistat (a NEDD8 inhibitor) have each been independently studied in hematologic malignancies and have tolerable safety profiles with limited single-agent activity. Preclinical studies in AML cell lines and primary AML cells show the combination to be highly synergistic, particularly in high-risk phenotypes such as p53 mutant and FLT-3-ITD positive cells. Here, we present the safety, pharmacokinetics and pharmacodynamics of belinostat and pevonedistat in a dose escalation Phase I study in AML and High-Risk MDS.MethodsEighteen patients (16 with AML, 2 with MDS) were treated at 5 dose levels (belinostat 800–1000 mg/m2, pevonedistat 20–50 mg/m2). Safety and tolerability were assessed according to protocol defined dose limiting toxicities (DLTs). Correlative pharmacokinetic and pharmacodynamic analyses were performed.ResultsNo dose limiting toxicities were noted. Most Grade 3 or 4 toxicities were hematologic in nature. The best response was stable disease in four patients, and complete remission in one patient who qualified as an exceptional responder. Pharmakokinetic studies revealed no association between drug exposure and best response. Pharmacodynamic RT-PCR studies demonstrated post-treatment increases in several proteins, including quantitative increases in the oxidative stress protein NQO1, ferroptosis protein SLC7A11, and GSR, linked to glutathione metabolism and oxidative stress, as did the anti-oxidants SRXN1 and TXNRD1.ConclusionsPatterns of post-treatment changes in correlative pharmacodynamic parameters may suggest possible mechanistic changes in the DNA damage response, oxidative damage, and ferroptosis pathways. The combination of pevonedistat plus belinosat is safe in an adult relapsed and/or refractory AML/High-Risk MDS population with modest but notable activity in this heavily treated, high risk population. Our findings also raise the possibility that certain extremely poor prognosis AML patients may respond to a regimen combining two targeted agents that have little or no activity when administered individually.Trial registrationClinicalTrials.gov ID NCT03772925, first posted 12/12/2018; CTEP Identifier 10246.

01 Jun 2025·STAR Protocols

Protocol for pull-down capture of ubiquitinated and NEDDylated liver proteins from transgenic biotinylated ubiquitin and NEDD8 mice

Article

Author: Zapata-Pavas, L Estefanía ; Delgado, Teresa C ; Martínez-Chantar, María Luz

Ubiquitination and NEDDylation post-translational modifications (PTMs) are important regulatory mechanisms in liver disease. Here, we describe a protocol for capturing ubiquitinated and NEDDylated proteins by pull-down assay in liver samples from transgenic mouse models of whole-body biotinylated ubiquitin/NEDD8. We describe steps for sample preparation samples, protein immobilization, pull-down assay, and sample final elution. The identification of the hepatic ubiquitome and NEDDylome allows a better understanding of the pathophysiological mechanisms underlying liver disease. For complete details on the use and execution of this protocol, please refer to Gil-Pitarch et al.¹.

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NEDD8

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