» Articles » PMID: 35463041

A Review on Cullin Neddylation and Strategies to Identify Its Inhibitors for Cancer Therapy

Overview
Journal 3 Biotech
Publisher Springer
Specialty Biotechnology
Date 2022 Apr 25
PMID 35463041
Authors
Affiliations
Soon will be listed here.
Abstract

The cullin-RING E3 ligases (CRLs) are the biggest components of the E3 ubiquitin ligase protein family, and they represent an essential role in various diseases that occur because of abnormal activation, particularly in tumors development. Regulation of CRLs needs neddylation, a post-translational modification involving an enzymatic cascade that transfers small, ubiquitin-like NEDD8 protein to CRLs. Many previous studies have confirmed neddylation as an enticing target for anticancer drug discoveries, and few recent studies have also found a significant increase in advancement in protein neddylation, including preclinical and clinical target validation to discover the neddylation inhibitor compound. In the present review, we first presented briefly the essence of CRLs' neddylation and its control, systematic analysis of CRLs, followed by the description of a few recorded chemical inhibitors of CRLs neddylation enzymes with recent examples of preclinical and clinical targets. We have also listed various structure-based pointing of protein-protein dealings in the CRLs' neddylation reaction, and last, the methods available to discover new inhibitors of neddylation are elaborated. This review will offer a concentrated, up-to-date, and detailed description of the discovery of neddylation inhibitors.

Citing Articles

Neddylation steers the fate of cellular receptors.

Park J, Lee M, Lee J, Moon G, Kim S, Chun Y Exp Mol Med. 2024; 56(12):2569-2577.

PMID: 39623094 PMC: 11671587. DOI: 10.1038/s12276-024-01358-0.


Neddylation Regulation of Immune Responses.

Mao H, Lin X, Sun Y Research (Wash D C). 2024; 6:0283.

PMID: 38434245 PMC: 10907026. DOI: 10.34133/research.0283.


Neddylation of insulin receptor substrate acts as a bona fide regulator of insulin signaling and its implications for cancer cell migration.

Park J, Moon G, Cho A, Kwon M, Park J, Yi E Cancer Gene Ther. 2024; 31(4):599-611.

PMID: 38272982 PMC: 11016467. DOI: 10.1038/s41417-024-00729-z.


Lysine deserts and cullin-RING ligase receptors: Navigating untrodden paths in proteostasis.

Szulc N, Piechota M, Biriczova L, Thapa P, Pokrzywa W iScience. 2023; 26(11):108344.

PMID: 38026164 PMC: 10665810. DOI: 10.1016/j.isci.2023.108344.

References
1.
Rambacher K, Calabrese M, Yamaguchi M . Perspectives on the development of first-in-class protein degraders. Future Med Chem. 2021; 13(14):1203-1226. DOI: 10.4155/fmc-2021-0033. View

2.
Barghout S, Schimmer A . E1 Enzymes as Therapeutic Targets in Cancer. Pharmacol Rev. 2020; 73(1):1-58. DOI: 10.1124/pharmrev.120.000053. View

3.
Hammill J, Scott D, Min J, Connelly M, Holbrook G, Zhu F . Piperidinyl Ureas Chemically Control Defective in Cullin Neddylation 1 (DCN1)-Mediated Cullin Neddylation. J Med Chem. 2018; 61(7):2680-2693. PMC: 5898815. DOI: 10.1021/acs.jmedchem.7b01277. View

4.
Zhou L, Jiang Y, Liu X, Li L, Yang X, Dong C . Promotion of tumor-associated macrophages infiltration by elevated neddylation pathway via NF-κB-CCL2 signaling in lung cancer. Oncogene. 2019; 38(29):5792-5804. DOI: 10.1038/s41388-019-0840-4. View

5.
Gai W, Peng Z, Liu C, Zhang L, Jiang H . Advances in Cancer Treatment by Targeting the Neddylation Pathway. Front Cell Dev Biol. 2021; 9:653882. PMC: 8060460. DOI: 10.3389/fcell.2021.653882. View