DCUN1D1 and neddylation: Potential targets for cancer therapy

Abstract

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.

Keywords: Cancer; Cancer therapy; DCUN1D1; E3 ligase; Neddylation.