Last update 01 Nov 2024

DCN1

Last update 01 Nov 2024

Basic Info

Synonyms

DCN1, DCN1-like protein 1, DCNL1

+ [10]

Introduction

Part of an E3 ubiquitin ligase complex for neddylation (PubMed:18826954). Promotes neddylation of cullin components of E3 cullin-RING ubiquitin ligase complexes (PubMed:26906416, PubMed:23201271, PubMed:19617556, PubMed:23401859). Acts by binding to cullin-RBX1 complexes in the cytoplasm and promoting their nuclear translocation, enhancing recruitment of E2-NEDD8 (UBE2M-NEDD8) thioester to the complex, and optimizing the orientation of proteins in the complex to allow efficient transfer of NEDD8 from the E2 to the cullin substrates. Involved in the release of inhibitory effets of CAND1 on cullin-RING ligase E3 complex assembly and activity (PubMed:25349211, PubMed:28581483). Acts also as an oncogene facilitating malignant transformation and carcinogenic progression (By similarity).

Drugs associated with DCN1

DI 1548

Target

DCN1

Mechanism

DCN1 inhibitors

Active Org.

University of Michigan

Originator Org.

University of Michigan

Active Indication

Chemical and Drug Induced Liver Injury

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SK-464

Target

DCN1 x UBC12

Mechanism

DCN1 inhibitors [+1]

Active Org.

Zhengzhou University

Originator Org.

Zhengzhou University

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

DI-1859

Target

DCN1

Mechanism

DCN1 inhibitors

Active Org.

University of Michigan

Originator Org.

University of Michigan

Active Indication

Chemical and Drug Induced Liver Injury

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with DCN1

100 Translational Medicine associated with DCN1

0 Patents (Medical) associated with DCN1

148

Literatures (Medical) associated with DCN1

01 Oct 2024·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

DCUN1D1 and neddylation: Potential targets for cancer therapy

Review

Author: Donaldson, Lara ; de Vasconcellos, Jaira F ; Zerbini, Luiz F ; Foret, Chiara L M ; Paccez, Juliano D

Cancer affects millions of people and understanding the molecular mechanisms related to disease development and progression is essential to manage the disease. Post-translational modification (PTM) processes such as ubiquitination and neddylation have a significant role in cancer development and progression by regulating protein stability, function, and interaction with other biomolecules. Both ubiquitination and neddylation are analogous processes that involves a series of enzymatic steps leading to the covalent attachment of ubiquitin or NEDD8 to target proteins. Neddylation modifies the CRL family of E3 ligase and regulates target proteins' function and stability. The DCUN1D1 protein is a regulator of protein neddylation and ubiquitination and acts promoting the neddylation of the cullin family components of E3-CRL complexes and is known to be upregulated in several types of cancers. In this review we compare the PTM ubiquitination and neddylation. Our discussion is focused on the neddylation process and the role of DCUN1D1 protein in cancer development. Furthermore, we provide describe DCUN1D1 protein and discuss its role in pathogenesis and signalling pathway in six different types of cancer. Additionally, we explore both the neddylation and DCUN1D1 pathways as potential druggable targets for therapeutic interventions. We focus our analysis on the development of compounds that target specifically neddylation or DCUN1D1. Finally, we provide a critical analysis about the challenges and perspectives in the field of DCUN1D1 and neddylation in cancer research. KEY POINTS: Neddylation is a post-translational modification that regulates target proteins' function and stability. One regulator of the neddylation process is a protein named DCUN1D1 and it is known to have its expression deregulated in several types of cancers. Here, we provide a detailed description of DCUN1D1 structure and its consequence for the development of cancer. We discuss both the neddylation and DCUN1D1 pathways as potential druggable targets for therapeutic interventions and provide a critical analysis about the challenges and perspectives in the field of DCUN1D1 and neddylation in cancer research.

01 Oct 2024·Odontology

Inhibition of DCUN1D1 attenuates periodontitis by suppressing NF-κB signaling

Article

Author: Qin, Jian ; Pan, Chao ; Su, Zhijian ; Li, Shuangjing ; Xie, Honghui ; Zou, Li

Nuclear factor kappa-B (NF-κB) signaling-mediated inflammation contributes greatly to the pathogenesis of periodontitis. Neddylation, a ubiquitin-like posttranslational modification, is known to regulate NF-κB signaling. DCUN1D1 (defective in cullin neddylation 1 domain containing 1) is a critical factor in neddylation and has been shown to regulate NF-κB activation. However, the previse roles of DCUN1D1 in periodontitis are not fully elucidated. To explore the roles of DCUN1D1 in periodontitis, the expression of DCUN1D1 was measured in gingival tissues of patients with periodontitis. We inhibited DCUN1D1 by siRNA knocking down or using inhibitor in gingival fibroblasts and the lipopolysaccharides (LPS)-induced expression of IL-6 and TNF-α, and activation of NF-κB were measured. The expression of DCUN1D1 was increased in gingival tissues of patients with periodontitis. Knocking down or inhibiting DCUN1D1 suppressed LPS-induced production of IL-6 and TNF-α, decreased NF-κB activity, and inhibited LPS-induced activation of NF-κB. Inhibiting DCUN1D1 ameliorates periodontitis by suppressing NF-κB signaling.

01 Oct 2024·International Journal of Biological Macromolecules

A comprehensive review on DCN1 protein, inhibitors and their therapeutic applications

Review

Author: Zhao, Wen ; Ma, Liying ; Yang, Feifei ; Qin, Tingting ; Zheng, Xiaoke ; Yuan, Ziqiao ; He, Zhangxu ; Zhang, Jingyu

DCN1, a critical co-E3 ligase in the neddylation process, mediates the activation of Cullin-RING Ligases (CRLs) by selectively catalyzing cullin neddylation, further regulating the activity of substrate proteins. It has been identified as an important target for human diseases, including cancers, fibrotic diseases, and cardiovascular disorders. This work aims to provide a perspective for the discovery of novel DCN1 inhibitors by the analysis of biological roles, protein structures, structure-activity relationships and design strategy disclosed in recent years. Additionally, we will discuss the current status, challenges and opportunities in hope of offering insights into the development of DCN1 inhibitors for human diseases.

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DCN1

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