E3 ubiquitin ligases: styles, structures and functions

Quan Yang,Dan Chen,Yang Wang,Jinyao Zhao

doi:10.1186/s43556-021-00043-2

Abstract

E3 ubiquitin ligases are a large family of enzymes that join in a three-enzyme ubiquitination cascade together with ubiquitin activating enzyme E1 and ubiquitin conjugating enzyme E2. E3 ubiquitin ligases play an essential role in catalyzing the ubiquitination process and transferring ubiquitin protein to attach the lysine site of targeted substrates. Importantly, ubiquitination modification is involved in almost all life activities of eukaryotes. Thus, E3 ligases might be involved in regulating various biological processes and cellular responses to stress signal associated with cancer development. Thanks to their multi-functions, E3 ligases can be a promising target of cancer therapy. A deeper understanding of the regulatory mechanisms of E3 ligases in tumorigenesis will help to find new prognostic markers and accelerate the growth of anticancer therapeutic approaches. In general, we mainly introduce the classifications of E3 ligases and their important roles in cancer progression and therapeutic functions.

Highlights

Almost all proteins in cells and some of the extracellular proteins are constantly updated through degradation and replacement with newly synthesized proteins
From this review, we have briefly illustrated the principles of ubiquitin system and the important role of E3 ligases in cancer progression
It’s worth noting that E3 ligases can function either as tumor promoters or suppressors

Summary

Introduction

Almost all proteins in cells and some of the extracellular proteins are constantly updated through degradation and replacement with newly synthesized proteins. The highly important function of the E3 ligase APC/CCdh1 is to regulate cell cycle, promoting the transition into G1 through targeting mitotic proteins for degradation [87]. APC/CCdh1 tends to promote cancer cells to adapt to immune response by destabilizing SPOP, as cullin 3-SPOP is the direct E3 ligase to target PD-L1 for degradation.

Results

Conclusion