# Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential

## TL;DR

This review explains how neddylation, a protein modification, contributes to cancer development and resistance to treatment, and explores new ways to target it for cancer therapy.

## Contribution

The paper provides a comprehensive overview of neddylation's role in cancer and proposes novel therapeutic strategies targeting NEDD8 modification.

## Key findings

- Neddylation regulates key cancer processes like protein stability and transcriptional activity.
- Cellular stressors like hypoxia and oxidative stress trigger neddylation in tumors.
- Targeting NEDD8 modification offers new cancer treatment possibilities.

## Abstract

Neddylation, a protein post-translational modification, regulates diverse molecular biological processes in tumors, governing protein stability, function, subcellular localization, and transcriptional activity. Thus, it plays an essential role in sustaining tumorigenicity and the hallmarks of cancer. In tumors, neddylation is triggered by various forms of cellular stress, involving hypoxia, oxidative stress, and tumor metabolites, all of which drive tumor initiation and progression. This review explores the critical regulatory mechanisms and pathological features of the neddylation cascade in terms of tumor malignant evolution and therapeutic resistance. Additionally, it examines therapeutic strategies targeting NEDD8 modification, offering novel avenues for innovative cancer treatments by disrupting this dynamic, reversible modification process.